In South Africa’s Western Cape province, interpersonal violence was identified among the key prevention priorities in the provincial government’s Burden of Disease (BoD) Reduction project. To date, there are no adequate systematic reviews of the full range of potential intervention strategies. In response, available data and the literature on risk factors and prevention strategies for interpersonal violence were reviewed with a view to providing policy makers with an inventory of interventions for application. Given the predominance of upstream factors in driving the province’s rates of interpersonal violence, efforts to address its burden require an intersectoral approach. Achievable short-term targets are also required to offset the long-term nature of the strategies most likely to affect fundamental shifts. Documentation and evaluation will be important to drive long-term investment, ensure effectiveness and enable replication of successful programmes and should be considered imperative by interpersonal violence prevention policymakers in other low- to middle-income contexts.