This article reviews recent developments in the pharmacotherapy of mood disorders. Pharmacotherapy is the best studied and most widely validated approach for acute phase treatment and prevention of relapse-recurrence for patients with major depression, dysthymia, and bipolar affective disorder. Antidepressants are also the mainstay of inpatient treatment and, when considered together with electroconvulsive therapy, represent the first line of treatment for the most severe and incapacitating forms of depression. Similarly, pharmacotherapy with mood stabilizers is the first line of treatment for bipolar depression and mania. Despite such efficacy, problems associated with pharmacotherapy include acceptability, tolerability, adherence, incomplete remission, and high rates of recurrence after drug discontinuation. Moreover, a small subset of patients do not respond to multiple medication trials.