Atypical antipsychotic drugs, by definition, differ from typical antipsychotic agents in producing significantly fewer extrapyramidal symptoms and having a lower risk of tardive dyskinesia in vulnerable clinical populations at doses that produce comparable control of psychosis. The atypical drugs differ from the typicals in their mechanism of action, but not all share the same mechanism. Many, but not all, atypicals have been found to improve cognitive function, which could be their most important advantage with regard to efficacy. Clozapine, the prototype of these agents, has been found to improve delusions and hallucinations in patients who fail to respond to other antipsychotic drugs, and to reduce the risk of suicide. These agents have been found to increase cortical dopamine and acetylcholine release, as well as have a variety of effects on the glutamatergic system not shared by the typical agents. Effects on neuronal survival and plasticity, together with decreased neurotoxicity, might also contribute to their clinical advantage over typical neuroleptic drugs.