Central to the book is Blazer’s own clinical thinking and his way of integrating new findings in the care of the individual patient. Late-life depression is a disease that tries the clinician’s skills to their limit. Psychiatry now believes that late-life depression is a disease with rather specific brain abnormalities, but seemingly less specific factors often play a devastating role in late life. Many depressed patients are medically ill, have lost cognitive abilities necessary for negotiating their environment, are unable to care for themselves, experience unanticipated indignities, and lose the sense of meaning in their lives. In some cases, the biological mechanisms of what was originally thought to be a nonspecific factor are clarified. For example, subcortical white matter abnormalities and executive dysfunction, one of its clinical expressions (1), may lead to depression by inducing disability (2), but a concomitant path to both depression and disability may be dysfunction of frontostriatal systems (3) resulting from white matter abnormalities. Blazer’s book serves as a guide to the role of each path in the depression of the individual patient by placing biological and psychosocial findings in the clinical and personal context of the individual patient.