Depressive symptoms and religious/spiritual (R/S) practices are widespread around the world, but their intersection has received relatively little attention from mainstream mental health professionals. This paper reviews and synthesizes quantitative research examining relationships between R/S involvement and depressive symptoms or disorders during the last 50 years (1962 to 2011). At least 444 studies have now quantitatively examined these relationships. Of those, over 60% report less depression and faster remission from depression in those more R/S or a reduction in depression severity in response to an R/S intervention. In contrast, only 6% report greater depression. Of the 178 most methodologically rigorous studies, 119 (67%) find inverse relationships between R/S and depression. Religious beliefs and practices may help people to cope better with stressful life circumstances, give meaning and hope, and surround depressed persons with a supportive community. In some populations or individuals, however, religious beliefs may increase guilt and lead to discouragement as people fail to live up to the high standards of their religious tradition. Understanding the role that R/S factors play in preventing depression, facilitating its resolution, or leading to greater depression will help clinicians determine whether this is a resource or a liability for individual patients.