The inheritance of substance use and abuse among adolescents was investigated in a sample of 626 male and female 17-year-old twin pairs. Both licit (tobacco) and illicit (e.g., marijuana, amphetamines) substance use and abuse was assessed and analyzed using standard biometric methods. The heritability of use and abuse of illicit substances was modest (25% or less), whereas the heritability of tobacco use and nicotine dependence was substantial (40% to 60%). There was no evidence that gender moderated the strength of genetic influences. Shared environmental influences were substantial for all substance use measures. The finding of greater genetic influence on the use and abuse of a licit substance than on the use and abuse of illicit substances suggests that inherited risk to drug abuse is considerably moderated by environmental control, at least in adolescence. The finding of significant environmental influences on all substance use measures underscores the importance of intervention on early adolescent substance use, a known predictor of adult substance abuse and dependence.