With advances in medical treatment and an aging population, there is an increasing global burden of advanced and life-limiting illnesses. Individuals living with these conditions may experience substantial distress related to disease progression, changes in important roles and life goals, loss of meaning, and uncertainty about the future, but there has been limited evidence to inform their psychotherapeutic care. Managing cancer and living meaningfully (CALM) therapy is a brief, evidence-based, semistructured intervention that provides a framework to address practical issues, such as navigating the health care system and treatment decisions, and existential issues, including finding meaning and hope in the face of mortality. CALM has been shown to alleviate and prevent depression and to facilitate preparation for the end of life among patients with advanced cancer. It is being adapted to other life-threatening illnesses and different cultural contexts and health care settings. Advocacy is needed to support such approaches for individuals living with advanced and life-threatening illness.