In this article we review the empirical literature on weight gain associated with neuroleptic drug use. Weight gain, which appears to be associated with an increase in appetite, is variable but likely to be larger initially and then plateau. Clozapine and low-potency phenothiazines are associated with the largest gains and molindone with weight loss, but the mechanism is not known. Amantadine and fenfluramine may reverse weight gain to some degree. Dietary fat seems to play an important role in obesity, and research is needed to increase the data base and elucidate possible mechanisms. Studies are also needed to evaluate preventive strategies and to determine which drugs are least likely to produce weight gain as well as which drugs could be added to a neuroleptic regimen to control weight.