This update reviews new evidence on HIV screening not included in the 2005 evidence synthesis. It focuses on evidence in non-pregnant, adults and adolescents who do not report risk factors and are evaluated in lower-prevalence (<1%), low-risk clinical settings (referred to in this report as ‘low-risk’ persons), because this is the population for which the USPSTF and the 2006 CDC recommendations are discordant. In the 2005 evidence review, we identified several key areas where additional evidence could strengthen the case for screening in low-risk populations. These include gaps in the research regarding uncertainties about the acceptability of routine voluntary screening in low-risk persons; the yield of targeted versus universal screening and optimal methods of risk assessment in low-risk settings; the impact on test uptake and follow-up of abbreviated or streamlined counseling methods and newer testing or sampling methods; and the effects of screening on HIV transmission rates. We therefore focused on studies that could help fill in these gaps. We also evaluated new evidence on the cost-effectiveness of routine HIV screening and studies on the frequency of testing.