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The emergence of biological psychiatry as a major mental health movement and theoretical point of view presents important issues for psychoanalytic psychology in conceptualizing and treating psychopathology. Psychoanalytic and biological perspectives on depression, as well as other disorders, are often seen as representing contradictory and mutually exclusive theoretical models. This paper critically reviews some of the primary research evidence for the biological psychiatric diagnosis of endogenous depression, and challenges the tendency to construe findings as a basis for discounting the role of psychogenic factors or the value of psychological treatment approaches. Brief attention is given to philosophical issues of reductionism and mind-body dualism, which pose serious conceptual problems for a biological model of psychopathology. The potential for viewing biological and psychological factors as complementary is considered. Freud's early effort to devise a psychogenic model of psychopathology recognized this potential and is reflected in his attempt to build a metapsychological bridge between physiological and mental phenomena. Psychoanalytic theory may provide the essential framework for incorporating both biological and psychological perspectives on depression.