Nicotine maintains tobacco addiction. Nicotine acts on nicotinic cholinergic receptors, which demonstrate diversity in subunit structure, function, and distribution in the nervous system, mediating the multiple actions of nicotine described in tobacco users. Nicotine addiction is more prevalent and more severe in people with a history of major depression, schizophrenia, or alcohol or other drug abuse problems. The cigarette is a highly efficient drug delivery system, delivering nicotine rapidly and in relatively high concentrations to the brain, a situation that optimizes the likelihood of self-administration. The severity of nicotine addiction can be as- sessed using the Fagerström Tolerance Questionnaire or the DSM-IV, but these instruments are imprecise predictors of the key behavior in addiction, which is the difficulty in stopping tobacco use when there are compelling reasons to do so.