The atypical antipsychotics are defined by improved tolerability in comparison with conventional antipsychotics. Specifically, the atypicals are substantially less likely to cause troubling extrapyramidal symptoms and prolactin elevation. This reduction in adverse effects (AEs) is attributed to their short duration of occupancy at dopamine-2 receptors in the central nervous system and a high degree of activity at serotonin receptors of various subtypes. The main AEs associated with the atypicals are weight gain and metabolic effects, including disturbances in glucose metabolism and a risk of induced diabetes. However, the atypicals are not interchangeable: the risk of incurring these effects is high with clozapine and olanzapine, moderate with risperidone and quetiapine (but perhaps increasing at higher doses), and minimal with ziprasidone and aripiprazole. The atypicals have proved useful as monotherapy in treating schizophrenia and in combination with other psychoactive agents in treating bipolar disorder. Because of their improved tolerability, the atypicals offer the prospect of improved compliance and reduced risk of relapse, thus decreasing costs by the need for less hospitalization.