This study reviews available information on the economics and efficacy of aflatoxin risk-reduction interventions, and it provides an approach for analysis of the cost-effectiveness of public health interventions to reduce aflatoxin-induced human disease. Many strategies have been developed to reduce aflatoxin or its adverse effects in the body. However, a question that has been under-addressed is how likely these strategies will be adopted in the countries that need them most to improve public health. This study evaluates two aspects crucial to the adoption of new technologies and methods: the costs and the efficacy of different strategies. First, different aflatoxin risk-reduction strategies are described and categorized into pre-harvest, post-harvest, dietary, and clinical settings. Relevant data on the costs and efficacy of each strategy, in reducing either aflatoxin in food or its metabolites in the body are then compiled and discussed. In addition, we describe which crops are affected by each intervention, who is likely to pay for the control strategy, and who is likely to benefit. A framework is described for how to evaluate cost-effectiveness of strategies according to World Health Organization (WHO) standards. Finally, it is discussed which strategies are likely to be cost-effective and helpful under different conditions worldwide of regulations, local produce and soil ecology, and potential health emergencies.