Empirical research indicates that males are more likely than females to be delinquent, yet it is unclear why this gender gap exists. This uncertainty can impede gender-responsive prevention efforts to implement programs that target the criminogenic factors most salient for each sex. However, information from experimental evaluations of gender differences in the effectiveness of prevention services can guide gender-responsive approaches. This article provides a systematic review of such literature. The results demonstrated some evidence of gender differences in the ability of community-based preventive interventions to reduce substance use, delinquency, and/or violence, although no clear patterns emerged regarding the types of programs that are most effective for each sex. In addition, some programs had similar effects on females and males and others evidenced harmful effects for one sex or the other. These findings suggest that practitioners should carefully review evaluation evidence prior to targeting females, males, or both sexes for prevention services.