Antipsychotic agents have been an important adjunct in the acute and at times prophylactic management of bipolar disorder patients. As a result of safety considerations, particularly the risk of tardive dyskinesia, there are concerns about their long-term use as adjunctive treatment. Although alternative agents have been proposed, some treatment-refractory cases may not respond as well to other regimens. This sub-group of patients has not been well characterized, but may result from overinclusive criteria in defining bipolar disorder. A comprehensive Medline search dating back to 1966 was conducted to identify published studies on antipsychotic utilization in bipolar disorder patients. We investigated the support for their use, and their effectiveness in this population, and attempted to define the group of patients requiring antipsychotic treatment. Additionally, we reviewed specific safety considerations, and suggested standards for their use in bipolar patients.