Nicole Kidman was originally cast as Meg Altman but had to leave the project after aggravating a hairline knee fracture originally sustained while filming Moulin Rouge!.

Jodie Foster replaced Kidman on short notice, stepping down as head of the awards jury at the 2001 Cannes Film Festival and having only a week to prepare before filming resumed.

Hayden Panettiere was originally cast as Sarah but left the project at the end of 2000 and was replaced by Kristen Stewart, for whom this was only her second feature film.

The role of Raoul was originally offered to Maynard James Keenan, whom Fincher had directed in A Perfect Circle's 'Judith' music video, but Keenan was too busy with Tool, so Dwight Yoakam was cast instead.

Forest Whitaker had actually studied the script and considered directing the film himself before declining and later being cast as Burnham; director Fincher told him to watch Key Largo and emulate Humphrey Bogart's character.

Cinematographer Darius Khondji was fired shortly after filming began due to a conflict over aspects of production, and was replaced by Conrad W. Hall.

Jodie Foster became pregnant five weeks into filming; production initially disguised her pregnancy with a heavy sweater, but studio executives disliked the dailies and suspended production until after she gave birth, then resumed with reshoots.

The seamless opening tracking shot took nine days to film but several months to complete in post-production, combining live footage with computer-generated imagery to simulate a camera moving freely through the house.

A single five-second shot of Meg dropping the medical kit was filmed over a hundred times to make it look accidental while keeping the kit in focus and frame.

After test audiences rated the SWAT-raid ending poorly and rebuilding the already-dismantled set would have cost $3 million, editors instead re-cut existing footage of Burnham to make him appear less sympathetic.