While prevalence rates for alcohol use and related disorders differ widely between adult men and women, male and female adolescents do not exhibit the same disparity in alcohol consumption. Previous research and reviews do not address the emergence of differences in drinking patterns that occur during late adolescence. Therefore, a developmental perspective is presented for understanding how various risk and protective factors associated with problematic drinking affect diverging alcohol trajectories as youth move into young adulthood. This review examines factors associated with risk for developing an alcohol use disorder in adolescent girls and boys separately. Findings indicate that certain biological (i.e., genetic risk, neurological abnormalities associated with P300 amplitudes) and psychosocial (i.e., impact of positive drinking expectancies, personality characteristics, and deviance proneness) factors appear to impact boys and girls similarly. In contrast, physiological and social changes particular to adolescence appear to differentially affect boys and girls as they transition into adulthood. Specifically, boys begin to manifest a constellation of factors that place them at greater risk for disruptive drinking: low response to alcohol, later maturation in brain structures and executive function, greater estimates of perceived peer alcohol use, and socialization into traditional gender roles. On an individual level, interventions which challenge media-driven stereotypes of gender roles while simultaneously reinforcing personal values are suggested as a way to strengthen adolescent autonomy in terms of healthy drinking decisions. Moreover, parents and schools must improve consistency in rules and consequences regarding teen drinking across gender to avoid mixed messages about acceptable alcohol use for boys and girls.