Considerable progress has been made in prevention science, and since reachi
ng a high in the late 1970s and early 1980s, overall substance use has decl
ined in the United States. However, for some populations a,rd substances, s
maller declines or even increased use has been observed. Notably, the tradi
tional gender gap in substance use has deer-eased substantially, and it has
disappeared completely for some substances, especially among younger cohor
ts. This article was written to integrate existing evidence on the relevanc
e of gender for substance use prevention research and to move the the field
by suggesting theoretical models that might inform future prevention resea
rch with girls. This article reviews the following: (a) trends in substance
use, (b) gender differences in risk factors, and (c) theoretical models de
emed relevant to substance use prevention among girls. Finally, recommendat
ions regarding needed research and prevention strategies that fake gender,
race, and ethnicity into account are provided.