Considerable progress has been made in antimalarial research; however, further studies are required to improve the efficacy of clinically available drugs, to develop new agents with superior activity and to avoid the emergence of resistance. In particular, efforts must focus on understanding the mode of action of antimalarial agents and on the mechanism by which the parasite Plasmodium falciparum impedes the action of these drugs. In this review, the current status of the antimalarial agents chloroquine and artemisinin is discussed, and the link between mechanism of action and resistance highlighted.