Following increased resistance of malaria parasites to conventional drugs in the malarial regions of the world, the WHO is promoting artemisinin-based combination therapy (ACT) for treating uncomplicated malaria. The objective of this report is to review the available scientific information on the efficacy, safety, resistance and policy implementation of ACT as it relates to sub-Saharan Africa since the Abuja 2000 Roll Back Malaria initiative. To achieve this, a Medline search was performed to identify scientific publications relevant to the review. The data reviewed indicated that ACT proved very effective in the treatment of uncomplicated Plasmodium falciparum malaria in the region. ACT was shown to be effective, safe and tolerable and no resistance has been detected so far. However, the major challenges to its widespread use in the region include its high cost, low drug quality and poor healthcare delivery systems, among others. It is absolutely imperative for sub-Saharan African countries to establish an effective national antimalarial drug policy which will provide safe, effective, high-quality, accessible and affordable antimalarial drugs such as ACT to the populations at risk of malaria but, at the same time, promote rational drug use in order to delay or prevent the development of antimalarial drug resistance.