The major aim of this study was to examine the role of social problem solving in the relationship between personality and substance use in adolescents. Although a number of studies have identified a relationship between personality and substance use, the precise mechanism by which this occurs is not clear. We hypothesized that problem-solving skills could be one such mechanism. More specifically, we sought to determine whether problem solving mediates, moderates, or both mediates and moderates the relationship between different personality traits and substance use. Three hundred and seven adolescents were administered the Substance Use Profile Scale, the Social Problem-Solving Inventory-Revised, and the Personality Experiences Inventory to assess personality, social problem-solving ability, and substance use, respectively. Results showed that the dimension of rational problem solving (i.e., effective problem-solving skills) significantly mediated the relationship between hopelessness and lifetime alcohol and marijuana use. The theoretical and clinical implications of these results were discussed. (Contains 2 tables and 2 figures.)