Dramatic changes have recently occurred in the availability of treatment options for bipolar illness. Second generation mood stabilizing anticonvulsants carbamazepine and valproate are now widely used as alternatives or adjuncts to lithium. High potency benzodiazepines are also used as alternatives to typical neuroleptics, and now atypical neuroleptics are demonstrating efficacy and better side-effects profiles than the typicals. Thyroid augmentation strategies and dihydropyridine L-type calcium channel blockers require further clinical trials to define their role. Putative third generation mood stabilizing anticonvulsants lamotrigine, gabapentin, and topiramate have unique mechanisms of action and deserve further systematic study, as does the potential role for nonconvulsive brain stimulation with repeated transcranial magnetic stimulation (rTMS). These and a host of other potential treatment options now require a new generation of clinical trials to help identify clinical and biological markers of response and optimal use alone and in complex combination therapeutic regimens.