This article takes a systematic approach to reviewing substance use prevention programs introduced in elementary school (K-6th grade). Previous studies evaluating such programs among elementary school students showed mixed effects on subsequent substance use and related psychosocial factors. Thirty published evaluation studies of 24 elementary school-based substance use prevention programs were reviewed. The study selection criteria included searching for program evaluations from 1980 to 2008. Among 27 evaluation studies that examined program effects on substance use, 56% (n = 15) found significant decreases. In addition, programs most often demonstrated effects on increasing negative substance use attitudes, increasing knowledge, decreasing perceptions of prevalence rates (i.e., descriptive norms), and improving resistance skills. These results have implications for the appropriateness and value of introducing substance use prevention programs to youth in elementary school. (Contains 4 tables.)