The purpose of this guide is to strengthen the capacity of HIV/AIDS program managers to design interventions that reduce adolescents' vulnerability to HIV by offering viable and effective livelihood options to supplant high-risk behaviors motivated by economic insecurity. It is designed to help PEPFAR (President's Emergency Plan for AIDS Relief) teams encourage the development of tailored interventions that combine economic empowerment components with other activities to prevent HIV infection among the target population. Following a presentation of gender terms and definitions, this guide describes what is known about economic vulnerability and HIV risk for adolescent girls, as well as gaps in our current knowledge. It then presents a menu of programming options that address the particular constraints faced by varying subpopulations of adolescent girls within the context of gender-based constraints and economic vulnerability. For example, the programmatic responses needed by young married girls may be quite different from those needed by rural, married out-of-school girls or urban girls who are unmarried and in school. This guide explains how to match appropriate program elements to the diverse needs and vulnerabilities that put different groups of adolescents at heightened risk of HIV transmission. A series of one- to two-page briefs summarize potential gender-based constraints and opportunities faced by different subpopulations of adolescents.