Affective disorders are among the most common disorders in psychiatry. They are generally classified according to the persistence and extent of symptoms and by the polarity of these symptoms. The two poles of the affective spectrum are mania and depression. Bipolar disorder is characterized by the presence of the mania or hypomania and often depression. Unipolar depression is defined by depression in the absence of a lifetime history of mania or hypomania. These differences are not merely categorical but have important implications for the prognosis and treatment of these conditions. Bipolar disorder, for example, is better treated using mood-stabilizing medication, whereas unipolar depression responds optimally to antidepressant medications. In addition, prognostically, unipolar depression may sometimes be limited to one episode in a lifetime, whereas bipolar disorder is typically a lifelong condition. The course of both conditions, however, is often chronic, and frequently patients can present with unipolar depression only to later develop manic symptoms. A thorough understanding of both conditions is therefore required to treat patients presenting with affective symptomatology. This chapter discusses the epidemiology, etiology and genetics, pathogenesis, diagnosis, and treatment of unipolar depression and bipolar disorder. Figures illustrate gray matter differences with lithium use and the bipolar spectrum. Tables list the pharmacokinetics of commonly used antidepressants and medications commonly used in the treatment of bipolar disorder. This review contains 2 figures, 2 tables, and 136 references.