Although lithium remains the treatment of choice for manic depression, it is now well recognized that 20%-40% of patients either do not tolerate the drug or their disease does not respond to it. This subgroup of patients accounts for a substantial majority of the morbidity that accompanies this illness. For this reason, alternatives to lithium therapy will have a significant clinical impact. In a great majority of cases, the rapid-cycling variant of this disorder accounts for the resistance to lithium treatment. Recently, a growing body of literature has suggested that several medications routinely used in the management of seizure disorders, particularly carbamazepine and valproate, have therapeutic mood-altering properties. These drugs have been evaluated in numerous drug trials using open, double-blinded, longitudinal, and (in the case of carbamazepine) randomized designs. The authors comment on the phenomenology of manic depression and review the literature on use of anticonvulsants in the management of lithium-resistant manic depression.