To systematically review and update evidence on the effectiveness of youth HIV/AIDS prevention interventions in sub-Saharan Africa (SSA) and to make evidence-based policy recommendations to guide efforts toward meeting the United Nations General Assembly Special Session HIV/AIDS goals. Recent evidence (January 2005-December 2008) on the effectiveness of interventions to improve reported sexual behavior and biological outcomes among youth in SSA was assessed using the Steady, Ready, Go! (SRG) approach and synthesized with an earlier SRG review (January 1990-June 2005). A total of 23 studies were included following screening of approximately 1,200 citations. School-based, adult-led, curriculum-based interventions showed clear evidence of reducing reported risky sexual behavior. Interventions in health facilities increased the use of services when made accessible and more youth-friendly. In geographically defined communities, both interventions specifically targeting youth and community-wide interventions reduced reports of risky sexual behavior. HIV prevention among youth is a top priority in SSA. The most promising interventions should be scaled-up now, with careful evaluation, while exploring supplementary interventions to impact HIV incidence. Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.