Addiction and rehabilitation appear frequently throughout Infinite Jest. Many of the young tennis players are addicted to drugs, while half of the story portrays the lives of people recovering in a rehabilitation center. Rather than being unusual or strange, addiction is a common fact of life for these characters. Drugs, alcohol, and a variety of other substances allow the characters to escape the crushing alienation of modern existence. The constant cycle of addiction and rehabilitation provides a template for the novel to describe and diagnose the ills of contemporary society. Everyone in the novel is addicted to something, and their struggles to deal with this addiction echo their struggles to survive.

Substance use is a constant issue for many of the characters. Don Gately is recovering from drug addiction, Joelle Van Dyne is ordered to a rehabilitation center after trying to kill herself with drugs, and Hal Incandenza is addicted to (and then struggles to give up) marijuana. Rather than these addictions defining the characters, however, the addictions become a shared bond. Joelle, like Don before her, discovers that talking about her addictions with others with the same experience helps her.