This is a review of the studies comparing unipolar and bipolar depression, with focus on the course, symptomatology, neurobiology, and psychosocial literatures. These are reviewed with one question in mind: does the evidence support diagnosing bipolar and unipolar depressions as the same disorder or different? The current nomenclature of bipolar and unipolar disorders has resulted in research that compares these disorders as a whole, without considering depression separately from mania within bipolar disorder. Future research should investigate two broad categories of depression and mania as separate disease processes that are highly comorbid.