This collective volume takes a fresh look at the psychiatric diagnosis of “major depressive disorder”, the disorder’s nature and its social meaning today. The heterogeneity of the conditions we call “depression” is so great that it raises difficult questions of individuation and identity. Major depression is one category of disorder in the DSM-5 and ICD-10, yet it is virtually universally agreed that the conditions that fall under that category constitute several different disorders caused by quite different etiologies. Similarly, depression varies across cultures in the way it presents, the way it is experienced, and the way it is valued or disvalued, so if it is so different, what makes it the same condition of “depression” that is being studied across cultures? Depression is the category of mental disorder most clearly recognized continuously since antiquity, yet it is also a category that has transformed and dramatically expanded during the twentieth century, so what makes it the same category over time? This is both a major intellectual challenge and a more immediate editorial challenge of explaining how the many diverse contributions to this volume could possibly be talking about a common topic. In attempting to provide an encompassing perspective, we acknowledge that some of the contributors to this volume may well disagree (and that at times we two disagree), and put forward the following thoughts in the spirit of offering one possible perspective among many.