The aim of this study was to carry out a comprehensive and systematic review of the literature on drug-use prevention with vulnerable young people. A search of electronic databases was conducted to find evaluations of prevention programmes targeted at high-risk young people and including illegal drug use as an outcome measure. Sixteen relevant studies were found that used a suitable quality of research design, involving at least a comparison group. The most common setting for these evaluations was in schools, where life-skills training interventions showed positive results in reducing drug use (at least in the short term). In the community an intensive multi-component intervention (the Children at Risk program) was the most effective. Across different settings the 11-13 age range appeared to be a crucial period for intervention with vulnerable young people. All of the sixteen studies included in the review were from North America and therefore there is a need for outcome evaluations of targeted drug prevention initiatives in the UK.