Reaching a correct differential diagnosis among patients with psychotic symptoms was especially important during the era of first-generation antipsychotics, when treatments for the different disorders varied in terms of adverse events and likelihood of response. The historical "overdiagnosis" of schizophrenia and "underdiagnosis" of bipolar disorder in the United States was blamed for an increased exposure to neuroleptics among patients who might have benefited from lithium. With the recognition that second-generation antipsychotics are useful in the treatment of both schizophrenia and bipolar mania, and that combining them with classic mood stabilizers such as valproate may results in increased efficacy, the field is witnessing a convergence of pharmacological approaches to the treatment of schizophrenia and bipolar disorder. Substantially more data is available regarding combination treatments for bipolar disorder than for schizophrenia, and appropriate diagnosis remains important in predicting prognosis, but until the precise pathophysiology of psychotic disorders can be elucidated, and specific targeted treatments crafted, we will continue to see similar blended treatments for these two disease states.