The introduction of needle and syringe programmes (NSPs) during the 1980s is credited with averting an HIV epidemic in the United Kingdom and Australia, but hepatitis C (HCV) incidence continues to rise among injecting drug users (IDUs). NSPs incorporating additional harm reduction strategies have been highlighted as an approach that may impact on HCV incidence. This systematic review sought to determine which approaches to the organisation and delivery of NSPs are effective. Fifteen databases were searched for studies published since 1990. Two reviewers screened all titles and abstracts, and data extraction and quality assessment of individual studies were undertaken independently by one reviewer and checked for accuracy by a second. Sixteen studies met the criteria for inclusion. Based on 11 studies there was no evidence of an impact of different NSP settings or syringe dispensation policies on drug injecting behaviours, but mobile van sites and vending machines appeared to attract younger IDUs and IDUs with higher risk profiles. Two studies of interventions aimed at encouraging IDUs to enter drug treatment reported limited effects, but one study found that the combination of methadone treatment and full participation in NSPs was associated with a lower incidence of HIV and HCV. In addition, one study indicated that hospital-based programmes may improve access to health care services among IDUs. Currently, it is difficult to draw conclusions on 'what works best' within the range of harm reduction services available to IDUs. Further studies are required which have a stated aim of evaluating how different approaches to the organisation and delivery NSPs impact on effectiveness.