Given renewed interest in the role of human action in the development of depression, I re-examine a tradition in the West which interpreted phenomena akin to the symptoms and signs of modern depression as "a spiritual disease." In medieval Europe, acedia was a vice, an undesirable trait of character acquired in the course of living a life. Persons suffering from the vice of acedia were implicated as agents in its development and to some extent responsible for overcoming it. In Part I of this paper, I note the contemporary interest of psychiatrists and others in this vice, consider the warrants for asserting that it is akin to some forms of depression, and recount, in brief, the history of this vice from the fourth to the fifteenth centuries. In Part II, I discuss how medieval scholars, confessors, and spiritual guides understood the question of responsibility for acedia and how they distinguished between this vice and melancholia. I argue that acedia was a vice that could be distinguished from melancholia and that, while akin to clinical depression, this vice should not be identified with depression. This investigation of and commentary on acedia is intended as a contribution to the contemporary discussion of the role of human agency in the development of depression and in its treatment.