{OBJECTIVE:} This study examined the impact of spirituality and religiosity on depressive symptom severity in a sample of terminally ill patients with cancer and {AIDS.METHODS:} One hundred sixty-two patients were recruited from palliative-care facilities (hospitals and specialized nursing facilities), all of whom had a life expectancy {\textless}6 months. The primary variables used in this study were the {FACIT} Spiritual {Well-Being} Scale, a religiosity index similar to those used in previous research, the Hamilton Depression Rating Scale {(HDRS),} the Karnofsky Performance Rating Scale, the Memorial Symptom Assessment Scale, and the {Duke-UNC} Functional Social Support {Questionnaire.RESULTS:} A strong negative association was observed between the {FACIT} Spiritual {Well-Being} scale and the {HDRS,} but no such relationship was found for religiosity, because more religious individuals had somewhat higher scores on the {HDRS.} Similar patterns were observed for the {FACIT} subscales, finding a strong negative association between the meaning and peace subscale (which corresponds to the more existential aspects of spirituality) and {HDRS} scores, whereas a positive, albeit nonsignificant, association was observed for the faith subscale (which corresponds more closely to {religiosity).CONCLUSIONS:} These results suggest that the beneficial aspects of religion may be primarily those that relate to spiritual well-being rather than to religious practices per se. Implications for clinical interventions and palliative-care practice are discussed.