This review focuses on the comparative safety and efficacy profile of nine atypical antipsychotic drugs (amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine), which may ultimately affect the therapeutic options available for patients with schizophrenia. These antipsychotic compounds differ markedly in their potential to impact a number of quality-of-life measures. Furthermore, their differential effects on anxiety disorders, treatment-resistant depressive illness, cognitive functions and manic disorders may influence the selection of atypical antipsychotics for conditions associated with schizophrenia. The possible relevance of these parameters in evaluating the risk/benefit equation and probable involvement of varying receptor mechanisms is also discussed.