Sub-Saharan Africa is faced with a crisis of rising levels of resistance to antimalarial drugs and few available and affordable alternatives. Combination chemotherapy, using two or more drugs with different mechanisms and sites of action together, is proposed as a mechanism for slowing the process of development of resistance. In Thailand, this approach has resulted in a sustained increase in the cure rate. Whether such an effect would be seen in Africa is not known. This article reviews the rationale behind combination therapy, the drugs available and the available evidence from combination therapy trials in Africa. Treatment of uncomplicated malaria in pregnancy and infants is also discussed.