This study used a representative community-based sample of men and women born in the San Francisco Bay Area in the 1920s to investigate the long-term relations between religiousness, spirituality, depression, and physical health. In late adulthood (age late 60s/mid-70s), religiousness buffered against depression associated with poor physical health, with highest levels of depression observed in the low-religiousness-poor-physical-health group. The buffering effect of religiousness was present after controlling for social support and was predicted longitudinally using religiousness scored in middle adulthood (age 40s)—a time interval of approximately 30 years. Spirituality, operationalized in terms of adherence to noninstitutionalized religious beliefs and practices, did not have the same buffering effect as religiousness. The findings are discussed with regard to the mechanisms underlying the salutary effect of religion on depression resulting from personal adversity.