Managing Cancer and Living Meaningfully (CALM) is a brief, semistructured individual intervention designed to alleviate distress and to promote psychological growth in individuals with advanced disease. This intervention emerged from a longitudinal program of research and from the theoretical traditions of relational, attachment, and existential theory. Through a process that supports affect regulation, attachment security, and reflective functioning, CALM focuses on four content domains: (1) symptom management and communication with health care providers; (2) changes in self and relations with close others; (3) spiritual well-being, sense of meaning, and purpose; and (4) preparing for the future, sustaining hope, and facing mortality. Caregivers are invited to one or more CALM sessions, during which communication, relational strengths and disruptions, and hopes and fears related to the present and to the future are addressed. Qualitative research has shown that the structure of CALM provides a safe place for cancer patients to explore their fears, to be seen in human terms, and to face the challenges and threats of advancing disease. Quantitative research has shown that compared to usual care, it leads to significantly greater reduction in and prevention of depressive symptoms and improvement in death preparation. Therapist skill in the delivery of CALM is developed through didactic and experiential workshops and by ongoing supervision.