The range of symptoms and clinical syndromes subsumed under the rubric "depression" is remarkably large. It covers the lay use of the word to describe transient sad feelings on the one hand and a devastating biological illness on the other. In consequence, society has failed to grasp that severe mood disorders do, in fact, represent life-threatening medical illness. In the present article, we outline the major historical and contemporary contributors to the present misapprehension of this severe illness and discuss the serious consequences for diagnosis, treatment, and clinical research. We suggest potential categorical and terminological revisions to current formulations of the disease and emphasize that being severely ill involves much more than is subsumed by the term "depression".