This updated systematic review assesses the effects of pharmacological interventions for drug-using offenders. Systematic review protocols and conventions of the Cochrane Collaboration were followed to identify eligible studies. Studies were pooled in a meta-analysis to assess the impact of pharmacological interventions on drug use and criminal activity. An economic appraisal was conducted. The search strategies identified 22 studies containing 4372 participants. Meta-analyses revealed a small statistically significant mean difference favouring pharmacological interventions relative to psychological interventions in reducing drug use and criminal activity. When comparing the drugs to one another there were no significant differences between those included (methadone versus buprenorphine, naltrexone and cyclazocine). Overall, the findings of this review suggest that methadone and naltrexone may have some impact on reducing drug use and reincarceration. Individual pharmacological drugs had differing (generally non-significant) effects. One study identified serious adverse events. Three studies reported cost and consequences information sufficient to conduct a full economic analysis but this was not comprehensive enough to be able to make judgements across all treatment options. Full economic analyses should be encouraged. The study findings were limited mainly to male adult offenders.