Religiosity and spirituality are concepts often considered means of reducing substance abuse and are employed in substance abuse recovery programs such as Alcoholics Anonymous. Substance abuse is a serious social problem in the United States, a country in which religiosity and spirituality have been subject to change and re-definition, especially since the social turmoil of the 1960s. This study utilized data from the 2004 General Social Survey to examine the effects of religiosity and spirituality on substance abuse and to understand that social bonding may mediate the effects of religiosity on substance abuse outcomes. Four substance abuse outcomes were examined: lifetime crack use, lifetime injection drug use, drinking problem in the past year, and illegal substance use in the past year. A three-stage multivariate logistic regression analysis was used to evaluate the effects of religiosity and spirituality on substance abuse outcomes as well the hypothesized mediating status of social bonding. The results show that, with few exceptions, religiosity was negatively associated with substance abuse. Further, social bonding variables did slightly mediate the negative relationship between religiosity and substance abuse. As expected, spirituality increased the odds of some measures of substance abuse after religiosity was controlled. Policy implications and further research are discussed.