The purpose of this review is to highlight some of the issues that need to be addressed to optimally use functional neuroimaging as a clinical tool to predict outcomes in substance use disorders. First, the importance of recognizing the clinical heterogeneity of the substance use disorders population is highlighted. We also emphasize that empirical and theoretical analyses support the idea that the courses of substance use disorders are relatively independent of the types of substance being used. Second, various approaches to the measurement and characterization of the longitudinal courses of substance use disorders are summarized. Third, predictors of outcomes are reviewed and their limitations are discussed. Within this context, we describe aspects of our work that focus on using functional magnetic resonance imaging to predict outcomes. Fourth, we discuss future directions, critical experiments, and the utility of functional neuroimaging as a clinical tool.