In a key-word Medline search on the Internet, 19 twin or adoption studies were found to have examined substance use in adolescent samples; 18 focused on the initiation or use of substances, and 1 examined abuse. Of the seven retrospective studies that used adult samples, six addressed problematic behaviors such as substance dependence. The studies yielded evidence of genetic influence on substance use (strongest for tobacco use), the use of tobacco and alcohol together, and the co-occurrence of disinhibited and substance-using behaviors. The strength of genetic influences was mitigated by religiosity (more religious, less genetic influence); age (older youths had greater genetic influence); substance (stronger for tobacco, weaker for alcohol); region (greater genetic influence in urban environments); gender (greater genetic influence in males); and measure of use (frequency of use being more genetically influenced than initiation of use). Shared environment contributed to adolescent substance use consistently across all adolescent samples, and common shared environmental factors influenced initiation into tobacco and alcohol use. Although parental alcohol use had a small influence on adolescent shared environment, sibling influences were substantial. Clinicians should thus be aware that genetic influences on substance use, abuse, or dependence, or associated antisocial behavior, are modifiable, as shown by the many contexts that modulate them. Study limitation and research implications are discussed. 4 tables and 35 references