Drug tolerance occurs when a subject's reaction to a drug (such as a painkiller or intoxicant) decreases so that larger doses are required to achieve the same effect. In addicted patients, the resulting pattern of uncontrolled escalating doses may lead to drug overdose.

Tolerance may be related to the familiarity of "drug onset cues". The body is conditioned to respond to environmental cues such as the sight of a needle, and actually produces the beginnings of physiological responses before the drug is introduced. If there is no actual drug that follows, or if the dose is too small to produce the expected effect, it can trigger intense cravings in the addict. This may explain why "just one drink", or even the sight or presence of familiar alcohol cues, can cause a relapse in a recovering alcoholic.

Tachyphylaxis is a medical term referring to the rapid development of drug tolerance.

See also:

• desensitization
• physiological tolerance
• physical dependence

In a different context, drug tolerance can refer to the lenient policies of a government or organization toward drugs that are considered illegal in other areas. For example, the distribution of marijuana has been legal in the Netherlands since the early 1970s, and the state of California continues to test the legality of its medical marijuana laws.

Drug intolerance is another social issue. Many law enforcement and civic agencies (such as schools and scouting groups) advocate a zero tolerance policy towards drugs, meaning that any infraction of existing laws and regulations will be punished, no matter how small.