Religion and spirituality (R/S) are patient-centered factors and often are resources for managing the emotional sequelae of the cancer experience. Studies investigating the correlation between R/S (eg, beliefs, experiences, coping) and mental health (eg, depression, anxiety, well being) in cancer have used very heterogeneous measures and have produced correspondingly inconsistent results. A meaningful synthesis of these findings has been lacking; thus, the objective of this review was to conduct a meta-analysis of the research on R/S and mental health. Four electronic databases were systematically reviewed, and 2073 abstracts met initial selection criteria. Reviewer pairs applied standardized coding schemes to extract indices of the correlation between R/S and mental health. In total, 617 effect sizes from 148 eligible studies were synthesized using meta-analytic generalized estimating equations, and subgroup analyses were performed to examine moderators of effects. The estimated mean correlation (Fisher z) was 0.19 (95% confidence interval [CI], 0.16-0.23), which varied as a function of R/S dimensions: affective R/S (z=0.38; 95% CI, 0.33-0.43), behavioral R/S (z=0.03; 95% CI, 20.02-0.08), cognitive R/S (z=0.10; 95% CI, 0.06-0.14), and ‘other’ R/S (z=0.08; 95% CI, 0.03-0.13). Aggregate, study-level demographic and clinical factors were not predictive of the relation between R/S and mental health. There was little indication of publication or reporting biases. The correlation between R/S and mental health generally was positive. The strength of that correlation was modest and varied as a function of the R/S dimensions and mental health domains assessed. The identification of optimal R/S measures and more sophisticated methodological approaches are needed to advance research.