Natural products have made a crucial and unique contribution to human health, and this is especially true in the case of malaria, where the natural products quinine and artemisinin and their derivatives and analogues, have saved millions of lives. The need for new drugs to treat malaria is still urgent, since the most dangerous malaria parasite, Plasmodium falciparum, has become resistant to quinine and most of its derivatives and is becoming resistant to artemisinin and its derivatives. This volume begins with a short history of malaria and follows this with a summary of its biology. It then traces the fascinating history of the discovery of quinine for malaria treatment and then describes quinine's biosynthesis, its mechanism of action, and its clinical use, concluding with a discussion of synthetic antimalarial agents based on quinine's structure. The volume then covers the discovery of artemisinin and its development as the source of the most effective current antimalarial drug, including summaries of its synthesis and biosynthesis, its mechanism of action, and its clinical use and resistance. A short discussion of other clinically used antimalarial natural products leads to a detailed treatment of other natural products with significant antiplasmodial activity, classified by compound type. Although the search for new antimalarial natural products from Nature's combinatorial library is challenging, it is very likely to yield new antimalarial drugs. The chapter thus ends by identifying over ten natural products with development potential as clinical antimalarial agents.