This chapter considers the loss of the will to live, the desire for hastened death, and suicidality in patients with advanced disease. The challenge of distinguishing the loss of the will to live as a manifestation of depression from nonpathological death acceptance is explored and the clinical implications of such distinctions are examined. The quantitative findings from our longitudinal research regarding the prevalence, trajectory, and correlates of the desire for death in patients with advanced cancer are presented. The qualitative findings from this research revealed three distinct dimensions of the desire for death, only one of which reflects the literal wish to end life. The role of Managing Cancer and Living Meaningfully (CALM) in alleviating death anxiety, in examining the desire for death, in enhancing death preparation, and in improving communication with healthcare providers is considered here.