The extent to which peer influences on substance use in adolescence systematically vary in strength based on qualities of the adolescent and his or her close friend was assessed in a study of 157 adolescents (age: M = 13.35, SD = 0.64), their close friends, and their parents assessed longitudinally with a combination of observational, analogue, sociometric, and self-report measures from early to mid adolescence. The degree to which adolescents changed their levels of substance use in accord with their peers’ baseline levels of use was predicted by a range of theoretically salient factors including: observed teen lack of autonomy and social support in prior interactions with mothers, low teen refusal skills, and the level of social acceptance of their close friend. Findings suggest the importance of both internal factors (e.g., autonomy and relatedness struggles) and external factors (e.g., social status of friends) in explaining why vulnerability to peer influence processes may be much greater for some adolescents than others.