Physical dependency on a substance is defined by the appearance of characteristic withdrawal symptoms when the drug is suddenly discontinued. While benzodiazepines, barbiturates, alcohol and nicotine are all well known for their ability to induce physical dependence, other drugs share this property that are not considered addictive: cortisone, beta-blockers and most antidepressants are examples. So while physical dependency can be a major factor in the psychology of addiction, the primary attribute of an addictive drug is its ability to induce euphoria while causing harm.

Some drugs induce physical dependence or physiological tolerance - but not addiction - for example many laxatives, which are not psychoactive; nasal decongestants, which can cause rebound congestion if used for more than a few days in a row; and some antidepressants, most notably Effexor and Paxil, as they have quite short half-lives, so stopping them abruptly causes a more rapid change in the neurotransmitter balance in the brain than many other antidepressants. Many non-addictive prescription drugs should not be suddenly stopped, so a doctor should be consulted before abruptly discontinuing them.

The speed with which a given individual becomes addicted to various substances varies with the substance, the frequency of use, the means of ingestion, and the individual. Some alcoholics report they exhibited alcoholic tendencies from the moment of first intoxication, while most people can drink socially without ever becoming addicted. Because of this variation, some people hypothesize that physical dependency and addiction are in large part genetically moderated. Nicotine is considered by many to be the most addictive substance in the world, although there has been no way found to determine this. Caffeine, ingested by more than 80% of human adults, is the most popular psychoactive substance in the world.