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Recently divorced from a rich pharmaceutical magnate, Meg Altman (Jodie Foster) and her 11-year-old daughter Sarah (Kristen Stewart), move into a 19th century brownstone in the Upper West Side of Manhattan. The former owner, a wealthy recluse, made some conversions to the house, including an elevator, a security system, and a panic room. Meg never really expects to use the panic room and, in fact, feels claustrophobic when in it. When the house is broken into that very night by three thieves—Burnham (Forest Whitaker) (who works for the security company that installed and monitors the security system for the house), Junior (Jared Leto) (grandson of the previous owner), and Raoul (Dwight Yoakam) (Junior's hired hand)—Meg and Sarah are forced to take refuge in the panic room. Unfortunately, the separate, secure telephone line is not yet hooked up, diabetic Sarah has no access to her medication, and neither of them know that there is millions of dollars hidden in a safe in the floor of the panic room, which is what the trio of thieves is after ...at all cost.

Panic Room is based on a screenplay by American filmmaker David Koepp, who also co-produced the movie.

A panic room, also known as a safe room, is a secure room with its own telephone line where residents can hide to protect themselves from a break-in, home invasion, or other threat. In Panic Room, the safe room was so well-fortified as to contain security cameras, a PA system, concrete and steel walls and floor, a four-inch-thick steel door, and its own ventilation system.

She didn't. Yes, insulin will reduce the amount of sugar in a person's blood. Many viewers, knowing that Sarah was a Type 1 diabetic and was suffering from hypoglycemia (low blood sugar), incorrectly conclude that she was injected with insulin. What she needed, and most likely received, was glucagon. Glucagon is essentially the opposite of insulin. Insulin causes the body to take the sugar into the cells and causes blood glucose to go down. Glucagon causes the liver to release its stored glucose into the blood, causing the levels to rise. The reason they give glucagon rather than drinking something like orange juice is because, when sugars are that low, there is a strong choking hazard, so it's not smart to give anything by mouth.

After convincing the two police officers that she's okay, Meg goes back into the house, picks up a sledge hammer, and begins to knock out all of the security cameras (causing the surviving thieves to wonder why they "hadn't thought of that"). Inside the panic room, Burnham has managed to open the safe and discovered $22 million in bearer bonds, not the $3 million Junior had originally led him to believe. He stuffs them inside his shirt, and he and Raoul (holding Sarah hostage) exit the panic room. They slowly make their way downstairs only to be met at the bottom by Meg's ex-husband Stephen (Patrick Bauchau) pointing a gun at them. Stephen orders them to let Sarah go, while Meg sneaks up behind and strikes Raoul with the sledge hammer, sending him crashing over the banister to the floor below and breaking his leg in the fall. Burnham takes this chance to flee, crashing through a large window onto the fire escape in the pouring rain. Meg notices Raoul crawling back up the stairs. Stephen tries to shoot him but misses. Raoul picks up the sledge hammer, knocks Stephen over, and attacks Meg. He wrestles Meg to the floor, holding her there until Sarah stabs him in the neck with hypodermic syringes from her diabetic kit. He knocks Sarah across the room, picks up the sledge hammer and is just about to bring it down upon Meg, when he is shot from behind by Burnham, who has returned to the house to ensure the Altmans weren't harmed by the murderous Raoul (and redeeming himself in the process; he was a [relatively] moral man: agreeing to the heist to help support his children and upon the contigent that no one be hurt during the robbery/burglary). Burnham then heads back outside, just as the SWAT team arrives, having been alerted by Officer Keeney (Paul Schulze) that there might be trouble at the Altman house. The police corner Burnham in the yard trying to climb over the fence and order him to come down and put up his hands, one of which is holding the bearer bonds. They order Burnham to show them his palms, and Burnham watches helplessly as the $22 million in bonds are blown away in the swirling rainstorm. In the final scene, Meg and Sarah are seated together on a park bench. Sarah is reading the want ads, looking for a new place to live. They finally settle on "West 33rd, two bedrooms, doorman building, park block, partial views, bright and cheery flat, high ceilings, wood floors."

Bearer bonds are unregistered securities. Whoever physically presents the bond will receive the payment, regardless of the original purchaser. No name is printed on the bond, and recovery of the value of a bearer bond in the event of its loss, theft, or destruction is usually impossible, though they are often insured. The same question in regards to an earlier movie is answered in slightly more detail here.