Un agente del FBI debe escoltar a un testigo desde Hawaii a Los Ángeles. Para intentar evitar que dicho testigo testifique, un asesino libera cientos de serpientes venenosas en el avión.
Banda sonora con las canciones del filme. Entre ellas, "Snakes On A Plane (Bring It)" (Cobra Starship), "The Only Difference Between Martyrdom and Suicide Is Press Coverage" (Panic! at the Disco), "Ophidiophobia" (Cee-Lo Green), "Queen Of Apology" (The Sounds), "Around The Horn" (The Bronx) o "Wine Red" (The Hush Sound).