According to director Bryan Bertino the film is partially based on an incident he experienced as a child. One evening, a stranger came to his door, asked for someone who wasn't there, and left. Later, Bertino found out that other homes in his neighborhood had been broken into that night.
Before filming any scene after The Strangers begin terrorizing the couple, Liv Tyler would have to run laps, do jumping jacks, and other physical activities to get her out of breath. This was so she would have the panicky feeling the real life characters would have been experiencing.
During filming, in order to get an actual reaction from Liv Tyler, Bryan Bertino would tell her where to expect a loud bang from, but would then have the loud noise come from a completely different direction.
Many theaters across the United States were sent faulty reels of the movie, containing sound problems, which made a few minutes to several scenes of the movie filled with nothing but static. Most movie-watchers didn't even realize the sound was a problem, since the dark overtone and loud background music at some areas make the static seem like part of the movie.
Arguably based on the 1981 Keddie Resort murders in northern California, although this has not been substantiated by anyone connected with the movie, with the writer claiming it is based on a childhood experience.
The trivia items below may give away important plot points.
According to Bryan Bertino and Liv Tyler, the finale had much more interaction and dialog between the victims and the strangers in the original script. It was cut to keep the intruders mysterious and eerie.
There were two special prosthetic makeups for Glenn Howerton. One of them was for fresh kill (which took 3 hours in the make-up chair), when he was shot in the face by Scott Speedman, and the other was for 1-hour-later prosthetics.