BACKGROUND: Physician-assisted suicide (PAS) is perhaps the most compelling and clinically relevant mental health issue in palliative care today. The desire for death, the consideration of suicide, the interest in PAS, and the relationship of these issues to depression and other psychosocial issues appear to be of paramount importance. METHODS: Psychiatric and psychosocial perspectives are used to understand the factors contributing to the interest in PAS, as well as to guide interventions in the clinical care of patients with advanced disease. RESULTS: Research and clinical experience suggest that attending to issues of depression, social support, and other psychosocial issues in addition to pain and physical symptom control are critical elements in interventions that are useful in reducing the distress of patients who desire hastened death. CONCLUSIONS: Psychosocial and psychiatric issues are among the most powerful predictors of desire for death and interest in PAS. Evaluation and intervention in these areas, particularly depression, is a critical component of compassionate care.