Having a purpose in life is strongly associated with well-being and quality of life. Some individuals develop their sense of purpose early in life and can sustain lifelong ideals. In contrast, we identify four transdiagnostic syndromes where purpose in life is impaired: 1) deficiencies in generating purpose; 2) loss of purpose due to traumatic events such as catastrophic illnesses or bereavements; 3) conflicts due to crossed purposes; and 4) maladaptive purposes, such as life-limiting single-minded goals, dominating others, or exacting revenge. Several psychotherapies associated with positive and existential psychologies help patients construct, reconstruct, or retain a sense of purpose. However, given the strong links between a sense of purpose and beneficial health and mental health outcomes, the authors suggest that many patients in psychiatric treatment including psychotherapies will benefit from attention to these issues. This article reviews approaches for assessing and addressing purpose in life in psychiatric treatment, to enhance patients’ healthy sense of purpose where this characteristic is impaired.