Although extensive research suggests that attention-deficit/hyperactivity disorder (ADHD) and conduct problems (CP; symptoms of oppositional defiant disorder, conduct disorder, and antisocial personality disorder) contribute to risk for substance use, why these symptoms increase risk for substance use remains unclear. Given that research indicates that perceived peer tolerance and perceived peer substance use affect substance use, we evaluated the degree to which these peer-perception constructs mediated the association that ADHD symptoms, CP symptoms, and their interaction share with substance use (i.e., alcohol use, marijuana use, and illicit drug use). Participants were college students (N = 627; 60% female; 47% European American) with a mean age of 20.23 years. Results indicated that perceived peer use significantly mediated the association of ADHD symptoms with alcohol, marijuana, and illicit drug use, whereas perceived peer use only mediated the association between CP symptoms and alcohol use. Perceived peer tolerance significantly mediated the association that both CP and ADHD symptoms had with marijuana use, but not alcohol or illicit drug use. Finally, CP symptoms moderated the indirect effect that ADHD symptoms had on alcohol use through perceived peer tolerance. At low levels of CP symptoms, increases in ADHD symptoms corresponded to increases in perceived peer tolerance, which was related to increased alcohol use. However, at high levels of CP symptoms, increases in ADHD symptoms corresponded to decreases in perceived peer tolerance, which was associated with decreased alcohol use. Implications of findings are discussed.