Second-generation (atypical) antipsychotics have become first-line medications for the treatment of schizophrenia and schizoaffective disorder, in large part due to their consistently reduced association with movement disorders and comparable efficacy to conventional agents. Direct comparisons among the atypical agents are, however, limited. In contrast to earlier atypical antipsychotic agents, ziprasidone and aripiprazole share a reduced propensity for weight gain and metabolic dysregulation. Given that obesity and dyslipidemia are highly prevalent and probable contributors to the elevated rates of morbidity and premature mortality among individuals with schizophrenia, these newer atypical agents offer the potential for improved health outcomes in this population.