Although the recurrent nature of manic depressive illness has been recognized since the time of Kraepelin, it has only recently been noted that this feature of the illness has prognostic significance. A subgroup of patients who experience more than four major mood swings per year has been identified as rapid cyclers and are now believed to account for a significant proportion of treatment resistance. In some instances, such rapid cycling is believed to be not only exacerbated by but possibly caused by the use of conventional unimodal antidepressants such as tricyclics. For this reason, the routine use of such antidepressants should be considered ill-advised until patients have been shown to be resistant to lithium's acute antidepressant properties. Although lithium remains the initial treatment of choice for manic depression, a substantial majority of manic depressive patients prove to be lithium-resistant and a growing body of data suggests this refractory group is accompanied by a disproportionate amount of frequent mood swings. When the lithium-resistant bipolar patient is encountered, the addition of one of two anticonvulsants, either valproate or carbamazepine, often provides significant therapeutic effects. Both valproate and carbamazepine appear to be similarly effective, but valproate may be better tolerated and easier to use.