Addiction to psychostimulant drugs such as nicotine, amphetamine, and cocaine is a serious public health problem for which there is a paucity of accepted forms of pharmacotherapy. Nicotine dependence has become more frequently associated with psychiatric illness in recent decades, and patients who have schizophrenia are at highest risk and have the poorest prognosis for stopping their addiction. Possible mechanisms for this association include self-medication, with nicotine attenuating attentional deficits and negative symptoms. Neurotensin has been postulated to be an endogenous neuroleptic, and the performance of neurotensin analogues in animal models of addiction makes such compounds intriguing candidates for treatment of addiction in high-risk psychiatric populations.