Physicians should recognize the importance of individual differences in the etiologic pathway to drug abuse. Drug use in most adolescents subsides or stops by adulthood; however, adolescents with behavioral or affective dysregulation, poor social skills, a limited social network, and substance abuse during late adolescence are at increased risk for substance dependence in adulthood. Research is needed, however, to clarify the developmental emergence and interaction between individual and contextual risk factors. Understanding person-environment processes within a developmental perspective not only yields a better understanding of the causes but also informs about taxonomy, prevention, and readiness to change and compliance in treatment and after-care. Treatment outcome research suggests that (1) relapse is likely to occur within the first 3 months after treatment completion and, to a lesser extent, over the year following treatment completion; (2) relapse is more likely in adolescents who have comorbid psychiatric disorders and other problems, such as high stress, low social skills, lack of involvement in productive activities or active leisure, and no follow-up intervention; (3) continued after-care treatment may maintain treatment gains; (4) the effectiveness of treatment and aftercare is likely to vary by the amount, mode, and the consistency with which it is delivered; (5) gender differences might have an impact on treatment outcome; and (6) adolescents presenting for treatment are likely to respond well to interventions based on family therapy and CBT approaches.