© 2015, Springer Science+Business Media New York. HIV infection rates continue to disproportionately affect Black men who have sex with men (Black MSM) compared to other groups. Research has shown that higher rates of substance use and higher levels of depression are positively correlated with higher sexual risk behavior, and little research has examined relationships between high levels of religiosity and spirituality prevalent in Black culture and issues of substance use and depression among Black MSM. This study did just that and found a relationship between religiosity, spirituality, and risk behavior. These relationships suggest that future HIV prevention models might incorporate religiosity and spirituality to increase the efficacy of risk reduction interventions for Black MSM.