Substance abuse is a major problem affecting the health and well-being of many people in our society. Although anecdotal evidence concerning linkages between learning disabilities (LD) and substance abuse has been common, this association is not well documented or understood. This article reviews the current research on substance abuse for adolescents and adults with LD, interpreting findings within a risk and resilience framework. Integrating these studies with the broader literatures on substance abuse and the needs of individuals with LD, the author develops hypotheses regarding specific risk and protective factors that could affect the occurrence of substance abuse for adolescents and adults with LD. Potential risk factors include a poor understanding of one’s disability, a lack of skills for developing peer relationships, and the need for prolonged family support. Future directions for research in relation to prevention of and intervention regarding substance abuse among individuals with LD are discussed.