Research over the past decade indicates that the prevalence of bipolar disorder is similar to that of major depression. The author discusses complexities in the diagnosis of bipolar disorder, especially in distinguishing bipolar from unipolar depression. Bipolar depression is associated with more mood lability, more motor retardation, and greater time spent sleeping. Early age of onset, a high frequency of depressive episodes, a greater percentage of time ill, and a relatively acute onset or offset of symptoms are suggestive of bipolar disorder rather than major depression. Because DSM-IV criteria require a manic or hypomanic episode for a diagnosis of bipolar disorder, many patients are initially diagnosed and treated as having major depression. Treatment of bipolar disorder with antidepressants alone is not efficacious and may exacerbate hypomania, mania, or cycling. It is important that clinicians be alert to any hint of bipolarity developing in the course of antidepressant therapy, especially among patients with first-episode major depression.