This review describes dosing strategies used to optimize the beneficial effects of atypical antipsychotic medications. Differences between manufacturers' recommended dosing and actual clinical practice are reconciled using evidence from pivotal double-blind randomized registration studies, other randomized clinical trials, case series, and case reports. With clozapine and perhaps olanzapine, plasma levels are correlated with therapeutic response; with risperidone, plasma levels are not correlated with therapeutic response but may be related to the occurrence of extrapyramidal symptoms. Information related to optimal dosing of quetiapine and ziprasidone is more limited. In clinical practice, the mean daily dose of risperidone has decreased, whereas that for olanzapine is increasing. The percentage of patients receiving quetiapine at doses above the manufacturer's recommended maximum is higher than would be expected, further illustrating that dosing ranges established during registration studies may not reflect the needs of day-to-day practice.