This study used stress coping theory to examine the effects of spirituality and religion on depression among a sample of Latino family members caring for a person with Alzheimer’s disease (AD) in the United States. Participants consisted of 209 Latino caregivers (CGs) drawn from baseline data from the Resource for Enhancing Alzheimer’s Caregivers Health (REACH) II clinical trial. The findings indicate that church attendance moderates the relationship between subjective forms of stress and depression in tandem with exhibiting direct effects on depression. Consistent with the central role religion plays in Latino culture, the results imply that religious involvement may play an important role in mitigating depression through indirect and direct pathways.