This dissertation is a modified systematic literature review of Freud’s (1920) contentious concept of a biological death instinct turned inward, including commentaries and criticisms. It begins with a brief clinical vignette introducing a masochistic terminally ill cancer patient. Freud argued that externalisation of the death instinct in the form of aggressive and destructive expression is necessary in order to protect against our primary impulse to self-destruction. Possible psychosomatic aetiology of biological disease as a form of self-destruction is explored in connection with the death instinct. The biological underpinnings of psychoanalytic phenomena that led Freud to hypothesise a death instinct are illuminated by recent advances in cell biology. Empirical studies on the effect suppression of emotions has on immune function and the discipline of psychoneuroimmunology is introduced to demonstrate the biological advantage of expressing emotions and as a way of conceptualising Freud’s theory of a death instinct. The implications for disease development and/or progression are discussed. The dissertation concludes by considering clinical implications of the death instinct.