Lithium is the treatment of choice for bipolar affective disorder. In a substantial proportion of patients, however, the response to lithium is inadequate, thus necessitating the use of additional or alternative medications. The increasing awareness of drawbacks associated with the agents most frequently employed--heterocyclic antidepressants and neuroleptics--lends support to the clinical necessity for identification of alternatives to or enhancement of lithium therapy. Over the past 10 years several treatments have been reported to be effective for at least some cases of bipolar affective disorder. This article reviews the rationale for such therapies and the data supporting the use of some of the more promising agents. Emphasis is given to three classes of treatment: anticonvulsants, thyroid hormone augmentation, and serotonergic agents.