The ability to sustain a sense of meaning is significantly associated with important elements of end-of-life despair. Meaning-centered group psychotherapy (MCGP), an eight-session group psychotherapy intervention, was developed to help patients with advanced cancer sustain or enhance a sense of meaning. MCGP has been shown to significantly improve spiritual well-being, sense of meaning, and quality of life and to diminish anxiety, depression, hopelessness, symptom burden distress, and desire for death. The mechanism of this benefit is through the enhancement of meaning. MCGP appears to be a beneficial intervention for emotional and spiritual suffering in advanced cancer patients. This chapter describes the theoretical framework and research basis for pursuing an intervention to enhance or sustain meaning. It also describes the development of MCGP, its evidence base for clinical efficacy, and outlines the intervention in great detail.