Abstract Although declining in the United States, tobacco addiction remains the most prevalent addiction of all drugs of abuse. Nicotine produces euphoria characterized by arousal and has a stimulant effect. Paradoxically, it also reduces perceived tension and stress. Nicotine also produces analgesia and decreases appetite. Nicotine smoke produces high carboxyhemoglobin levels and contains significant amounts of carcinogens that have been linked to the toxic effects of smoking. Much information has been gleaned from animal work about the neurobiology of the acute reinforcing and stimulant effects of nicotine. The neurobiological bases for the dependence-inducing properties of nicotine involve within-system decreases in reward-related neurotransmitter function, in a similar manner to other drugs of abuse. At the molecular level, differential receptor desensitization may underlie negative reinforcement, in which self-medication is used to control the functional recovery of nAChRs. At the neurocircuitry level, decreases in dopaminergic neurotransmission in the ventral tegmental area and nucleus accumbens are associated with the malaise associated with acute nicotine withdrawal. These changes may alter gene expression and trigger long-term neuroadaptive responses that are similar to other drugs of abuse.