Ten-year-old Lilith "Lily" Sullivan (Jodelle Ferland) is the seemingly innocent victim of two crazy parents—Edward (Callum Keith Rennie) and Margaret (Kerry O'Malley) Sullivan—who are suspected of abusing her. When her teacher notices that Lily's grades have plummeted from As to Ds and that she keeps falling asleep during class, she files a report with Child Protective Services, and Lily's case (no. 39) is assigned to social worker Emily Jenkins (Renée Zellweger), who quickly bonds with the little girl. One night, Emily gets a frantic phone call from Lily, claiming that she's afraid her parents are going to harm her. Emily dashes over and saves Lily from being baked in the oven. Vowing not to allow Lily back into the custody of her parents, Emily petitions to have custody of her until a suitable foster home can be found. Lily begins to improve under Emily's care, and Emily is certain that she's saved the poor child ...until it becomes apparent to Emily that Lilith is not the innocent child she appears to be.

Case 39 was filmed from a screenplay by screenwriter Ray Wright.

Lily couldn't sleep at home because she feared that her parents would try to kill her while she was sleeping, the time during which she was most vulnerable.

Edward explains (through his wife) that he doesn't like to speak when he's angry. One explanation is that Edward, knowing how Lily "feeds" on anger and fear, refused to feed her. A second possibility is that Lily ordered him not to speak to Emily under threat of retribution.

The movie doesn't directly answer that question. At one point, Edward tells Emily that it started from the day Lily was born. A person's soul supposedly enters the body at the moment they are born, he explains. It's Edward's guess that a demon soul entered into Lily's.

Since the movie ends at this point, the source of the bubbles is unknown. One theory is that the bubbles were supposed to suggest that Lily survived. A second theory is that Lily perished, and the bubbles were simply the result of the last pockets of air released from the car.

An alternate ending can be found on the DVD as a deleted scene in the Special Features section. In the alternate ending, Emily careens through the harbor gate and drives the car off the pier into the Bay just as in the theatrical ending. The car sinks to the bottom and fills with water. Suddenly, a man swims down to the car, opens Lily's door, and carries her to the surface, leaving Emily behind. Emily tries unsuccessfully to open her door but begins to pass out. Suddenly, the man reappears and frees her, too. As the ambulance carries Emily away, a news broadcast details the event. Margaret Sullivan can be seen watching it. In the final scenes, Emily frantically pleads with her lawyer to tell her where Lily is, while Lily arrives at the home of her new foster family.

Often times, trailers are produced and edited long before a movie is finished. This might explain why some scenes in the trailer can mislead the viewer. The scenes in the trailer that are exempt from the final production are: (1) Homeless man with shopping cart with a distorted demonic face, (2) Lilly sinking into bed (enforcing she is actually in danger of an external force, where in the movie she evolves quickly), (3) Emily and Lilly running towards Emily's room. They both look back and the door slams (once again enforcing an alternate storyline); (4) Emily cradling Lilly whilst screaming "Go Away!", (5) Detective Barron falling from building, (6) Emily once again cradling Lilly screaming "Leave her alone!", and (7) Emily holding Lilly under the bed while telling her to "Shh" and covering her mouth. They are both looking up and a demonic growl is heard (enforcing external danger.

Other movies that feature children who are not the little innocents they seem to be include The Bad Seed (1956) (remake The Bad Seed (1985)), Orphan (2009), The Omen (1976) (remake The Omen (2006)), Village of the Damned (1960) (remake Village of the Damned (1995)), and The Good Son (1993).