John Brown is a humble, but clumsy security guard working at the Bradford robotics laboratory in Riverton, Ohio, run by Artemus Bradford and his daughter Brenda, whom Brown has a crush on. Brown wishes to become a police officer, with support from his niece Penny. Brenda and Artemus create a lifelike robotic foot as part of the Gadget Program, to create cybernetically augmented police officers. Tycoon Sanford Scolex attacks the lab, steals the foot, and has Artemus murdered before escaping in his limo. Brown goes chasing him down in his car, which leads to its being destroyed by Scolex's explosive cigar leaving brown for dead, but a bowling ball coming from the fiery blast of Brown’s destroyed car smashingly crushes Scolex's hand, forcing him to replace it with a mechanical claw.
Robin Monroe, a New York journalist working for Dazzle, a fashion magazine, is invited by her boyfriend Frank to spend a week holidaying with him on the island paradise of Makatea, in the South Pacific. The final leg of their journey to Makatea is in a small dilapidated aircraft, piloted by middle-aged American Quinn Norris. They are accompanied by Quinn's girlfriend and co-pilot Angelica.
Ricky Hayman (Jeff Goldblum) and Kate Newell (Kelly Preston) work at the (fictional) Good Buy Shopping Network, a home shopping channel run by John McBainbridge (Robert Loggia). Sales have been down over the last two years under Ricky's management, and Kate was brought in to come up with new ideas. Ricky views Kate as a threat and she expresses her dislike for him as well. However, John has given Ricky an ultimatum to increase sales, or lose his job.
A Senate Armed Services Committee interviews a candidate for the position of Secretary of the Navy. Senator Lillian DeHaven (Anne Bancroft) from Texas criticizes the Navy for not being gender-neutral. Behind the curtains, a deal is struck: If women compare favorably with men in a series of test cases, the military will integrate women fully into all branches of the Navy.
Scott Roper (Eddie Murphy) is the best hostage negotiator in San Francisco. His girlfriend Veronica "Ronnie" Tate (Carmen Ejogo) is a newspaper reporter.
Professor Philip Brainard (Robin Williams) of Medfield College is developing a new energy source, in an attempt to raise enough money to save the college from closure. His preoccupation with his research distracts him from his fiancée, the college president Sara Jean Reynolds (Marcia Gay Harden). He has missed two weddings because of that preoccupation, much to Sara's anger. On the day of the third attempted wedding, Philip is approached by his former partner Wilson Croft (Christopher McDonald), who has profited from ideas he has stolen from the chemist and now desires to steal Sara from Philip and make her his wife, which he declares directly to Philip. Before he can make it to the wedding, his latest experiment shows fast development, forcing him to miss another wedding. The resulting substance created from the experiment is a green goo that increases in speed as it bounces and proves to be difficult to control, wreaking havoc on the neighborhood before the professor finally manages to capture it. Weebo (voiced by Jodi Benson), Philip's hovering robot assistant, classifies the substance as "flying rubber", leading Philip to christen it as "Flubber".
Joe Waters (Pesci) and Gus Green (Glover) are bumbling yet happy best friends who live modestly in New Jersey and have known each other since childhood. They share the hobby of fishing and win a stay in the Florida Everglades to go angling, but promise to return home in time for Thanksgiving.
Professional assassin Martin Blank finds himself depressed, disenchanted and bored with his work. A major problem is his chief rival Grocer, whose effort to cartelize the hitman business puts him at potentially lethal odds with the unaccompanied Martin. Following a botched contract, Martin receives an invitation to his 10-year high school reunion in his hometown of Grosse Pointe, Michigan. Initially reluctant to attend, he is pressured into it by both his therapist, Dr. Oatman, and his secretary, Marcella. She books him a contract in Michigan that coincides with the reunion, ostensibly to smooth things over with the client whose contract was botched.
NASA is training for the first manned mission to Mars by the spacecraft Aries. Due to a supposed glitch in the computer navigation system, NASA looks for the original programmer of the software to see why the software seems to be broken. Fred Z. Randall (Harland Williams), the eccentric programmer who wrote the software, meets Paul Wick (Jeffrey DeMunn), the flight director of the Mars mission; William "Wild Bill" Overbeck (William Sadler), the commander of the Mars mission; and astronaut Gary Hackman (Peter Onorati), the computer specialist. After a display of hard-headed stubbornness by Gary, he is hit in the head by a model of the Pilgrim 1 Mars lander, resulting in a skull fracture. NASA decides to replace him instead of delaying the mission. Fred is brought to NASA to see if he has what it takes to be an astronaut; he, along with Gordon Peacock, go through a series of exercises, which sees Fred do well, even going as far to break every record that Bill had. In the end, Fred gets the job.
A prologue introduces us to Dr. Austin Sloper (Albert Finney), a New York City doctor and resident of a large house on Washington Square whose wife dies in childbirth, leaving a daughter, Catherine (Jennifer Jason Leigh), to be raised by her father. As a child, Catherine is overweight, clumsy, and untalented; however, she is also a sweet, affectionate child. She adores her father and tries hard to please him, but he considers her a disappointment and treats her with ironic condescension. His thoughts are still much occupied with his beloved wife and with a promising son who died before Catherine was born, and he privately – but bitterly – resents his only surviving child for causing his wife's death.
In a small western Massachusetts town, Dr. Carolyn Ryan (Meryl Streep) and her sculptor husband Ben (Liam Neeson) seem to live an idyllic life with their two children Jacob (Edward Furlong) and Judith (Julia Weldon). Their world is shattered one evening when Sheriff Fran Conklin (Daniel von Bargen) arrives to tell them that Martha Taverner has been killed and witnesses saw Jacob with her just before she died. When he asks to speak with Jacob, the family realizes that he's not in his room as they thought. Conklin asks to look at Jacob's car, but Ben refuses to allow it. When Conklin tries to ask Judith where Jacob is, Ben becomes openly hostile, demanding the sheriff get a warrant.
Josie Potenza is the trophy wife of workaholic Hollywood producer Tony Potenza, but their marriage is crumbling due to his increased drinking resulting from stress at work. She convinces him to join her for a romantic getaway at a secluded lakeside cabin, but when it becomes obvious his concerns about the studio are going to take precedence over relaxation, she grudgingly tells him to return home but decides to stay on her own for a few days.
Best friends for life, gym teacher Mike O'Hara (Daniel Stern) and plumber Jimmy Flaherty (Dan Aykroyd) are united by their love of Boston and its sports teams, especially the Boston Celtics, who are playing their last season in the old Boston Garden. When the Celtics drop Game 6 of the NBA Finals to the Utah Jazz, setting up a deciding Game 7 in Boston, Mike and Jimmy find themselves depressed and hopeless. On top of all this, Mike has moved back in with Jimmy after his wife Carol, fed up with his unhealthy obsession with the Celtics, left him and took their son Tommy with her. Jimmy and Mike stumble upon the Jazz's selfish, one-man-show shooting guard Lewis Scott (Damon Wayans) at a Boston nightclub. Hoping at first to get him drunk enough so he'll be hungover for Game 7, Mike and Jimmy pose as Utah fans. This however leads to them running into their idol Larry Bird (as himself), who scolds them for being what he thinks are "fair weather" fans. However, the pair get more than they bargained for when the next morning they end up kidnapping Scott after he wakes up at Jimmy's apartment. The two decide to hold Scott until after the game, reasoning that if they are going to prison, they might as well help the Celtics win in the meantime.
Sam Simms (Sinbad) is a Secret Service agent assigned by his superior Wilkes (Robert Guillaume) to protect President Paul Davenport's (James Naughton) rebellious 13-year-old son Luke Davenport (Brock Pierce) after Luke's behavior causes another agent Woods (Timothy Busfield) to be replaced for mistreating Luke in front of media cameras. Woods is later fired for failing his physical. Simms sees this assignment as undesirable, but a possible stepping stone to protecting the President. He fails to connect with the boy at first, and Luke continues to misbehave, including an incident where he releases his pet snake Poison into a White House party. After seeing Luke get beat up by the school bully Rob (Zachery Ty Bryan), Simms feels sorry for him - he had felt alone as a teenager, too (losing his father in Vietnam) - and they become friends. Simms, a former boxing champion, agrees to sneak Luke out against the wishes of the chief of security Morton (Art LaFleur) and teach him how to fight.