Adolescents in sub-Saharan Africa are among the most vulnerable to HIV. Those who reside in households most affected by AIDS are often the most poor and socially disconnected; and many have also been orphaned by one or both parents. Many OVC and youth HIV programmes do not reach these adolescents in meaningful ways. In addition, most programmes do not address the crucial link between orphanhood status, HIV risk, and the need for social and economic support to mitigate their life circumstances. This is especially true for young females, who generally have greater social, economic and health vulnerabilities, and fewer protective assets in these environments. This article highlights research findings that identify the contribution of social capital, poverty, and orphan status to the adolescent experience in the wake of HIV/AIDS, and consequently, to better inform policies and programmes that target and attend to the needs of young people most at risk.