Flying at 40,000 feet in a cavernous, state-of-the-art 474 aircraft, Kyle Pratt (Jodie Foster) faces every mother's worst nightmare when her six-year-old daughter, Julia, vanishes without a trace mid-flight from Berlin to New York. Already emotionally devastated by the unexpected death of her husband, Kyle desperately struggles to prove her sanity to the disbelieving flight crew and passengers while facing the very real possibility that she may be losing her mind.

While neither Captain Rich (Sean Bean) nor Air Marshall Gene Carson (Peter Sarsgaard) want to doubt the bereaved widow, all evidence indicates that her daughter was never on board resulting in paranoia and doubt among the passengers and crew of the plane.

Finding herself desperately alone, Kyle can only rely on her own wits to solve the mystery and save her daughter.