Abstract: Objective To examine the effectiveness of needle exchange programs (NEPs) in modifying HIV-related outcomes in injection drug users (IDUs). Methods On-line computer searches of six electronic databases, hand searches of core journals and relevant studies, combined with key informant suggestions at the federal and front line level for potentially relevant studies, and review of local and community publications, resulted in the retrieval of 84 studies from 1997 to 1999 related to the effectiveness of needle exchange programs. The HIV-related outcomes of interest examined were behavioural (modifications in HIV-risk-related injection practices) and end-point physical health status outcomes (changes in rates of HIV, hepatitis B (HBV) and hepatitis C (HCV) seroprevalence or incidence) at either the population (most frequently, city; less frequently, country) or individual level. Results Relevance and quality assessment reviews resulted in the inclusion in this review of 21 relevant but largely methodologically weak primary studies. From the evidence of these primary studies, NEPs appear to continue to be effective in modifying most HIV risk-related injection practices although engagement in sharing drug preparation equipment continues. The earlier protective effect of NEP attendance against HIV, HBV and HCV seroconversion has not been consistently sustained. However, NEPs appear to be effective in attracting a group of IDUs experiencing higher HIV risk conditions and who are thereby at increased risk for HIV infection. Conclusions NEPs appear well positioned, as an accessible service, to continue to offer the knowledge and the means to modify engagement in HIV-risk-related injection practices. Enhanced programming is needed to address the documented continued sharing of injection preparation equipment, to modify engagement in a potentially effective, yet largely unrecognized, method of HIV transmission. The potential role of NEPs to expand and diversify as an acceptable comprehensive health resource for a marginalized group of people for whom mainstream health care has not always been easily accessible must be realized.