Abstract: The treatment of mood disorders has been an active field of research for over 50 years. Antipsychotics have been used primarily during the acute phase of the illness as an adjunct to mood stabilizers to rapidly stabilize patients and often discontinued when a patient's mood has stabilized and the risk for rapid relapse is deemed low. However, new evidence suggests that antipsychotics have a role in the maintenance therapy of some patients with bipolar disorders, particularly atypical antipsychotics, which pose a lower risk for tardive dyskinesia and other movement disorders than do conventional agents such as haloperidol. Aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone have US Food and Drug Administration (FDA) approval for the treatment of manic and mixed bipolar episodes. Quetiapine has FDA approval for the treatment of acute bipolar depression. Although 5 SGAs are approved for treating bipolar disorder, clinicians have little evidence on treatment adherence to assist in long-term dosing strategies. The use of second-generation antipsychotics (SGAs) in mood disorders is broadening, and this article presents presented diverse findings of the latest studies.