Nicotine addiction is a complex behavioral phenomenon comprising effects on several neural systems. Recent studies have expanded initial observations that the actions of nicotine on dopaminergic systems increase dopaminergic activity and release, leading to nicotine-induced reinforcement. Indeed, the actions of nicotine on many systems, including brainstem cholinergic, GABAergic, noradrenergic, and serotonergic nuclei, may help to mediate nicotine effects related to addiction. Furthermore, studies of mice lacking nicotinic acetylcholine receptor subunits or expressing supersensitive forms of these subunits have begun to tie together the molecular, neurochemical, and behavioral effects of nicotine. The use of multiple techniques by many laboratories provides optimism that the field is advancing toward elucidating the basic mechanisms of nicotine dependence.