Joel Barish, heartbroken that his girlfriend underwent a procedure to erase him from her memory, decides to do the same. However, as he watches his memories of her fade away, he realises that he still loves her, and may be too late to correct his mistake.

One day at work, unsuccessful puppeteer Craig finds a portal into the head of actor John Malkovich. The portal soon becomes a passion for anybody who enters its mad and controlling world of overtaking another human body.