Although optimism, social support, religiousness, and spirituality are important predictors of adjustment, rarely have studies examined these variables simultaneously. This study investigated whether optimism and social support mediated the relationship between religiousness and adjustment (distress and life satisfaction) and between spirituality and adjustment. Findings indicate that the relationship between intrinsic religiousness and life satisfaction and between prayer fulfillment and life satisfaction was mediated by optimism and social support. Furthermore, the relationship between religiousness and adjustment varied depending on how religiousness was operationalized and whether positive versus negative adjustment indicators were used. That is, intrinsic religiousness and prayer fulfillment were associated with greater life satisfaction, but extrinsic religiousness was not associated with life satisfaction. These findings were significant even after accounting for covariates (age, gender, ethnicity, social desirability). Results suggest religiousness and spirituality are related but distinct constructs and are associated with adjustment through factors such as social support and optimism.