In 2006, the World Health Organization issued a position statement promoting the use of indoor residual spraying (IRS) with dichlorodiphenyltrichloroethane (DDT) for malaria vector control in epidemic and endemic areas. Other international organizations concurred because of the great burden of malaria and the relative ineffectiveness of current treatment and control strategies. Although the Stockholm Convention of 2001 targeted DDT as 1 of 12 persistent organic pollutants for phase-out and eventual elimination, it allowed a provision for its continued indoor use for disease vector control. Although DDT is a low-cost antimalarial tool, the possible adverse human health and environmental effects of exposure through IRS must be carefully weighed against the benefits to malaria control. This article discusses the controversy surrounding the use of DDT for IRS; its effective implementation in Africa; recommendations for deployment today, and training, monitoring, and research needs for effective and sustainable implementation. We consider the costs and cost effectiveness of IRS with DDT, alternative insecticides to DDT, and the importance of integrated vector control if toxicity, resistance, and other issues restrict its use.