Bipolar disorder is one of the most severely debilitating of all medical illnesses, and is increasingly recognized as a major public health problem. For many patients with bipolar disorder, current pharmacotherapy is insufficient. Exciting recent data suggest that regulation of signaling molecules may be involved in the pathophysiology of the disorder, and in the mechanisms of action of mood stabilizers and antidepressants. Through our developing understanding of the biochemical targets of effective medications, several potential targets for new therapies have emerged. This short review will focus on two of the most promising such targets: glycogen synthase-3 and protein kinase C.