Malaria remains one of the major infectious diseases with high morbidity and mortality in developing and under-developed countries of the world. Although readily curable, the development of resistance by the malaria parasite especially Plasmodium falciparum, to existing antimalarials necessitates the need for continuous search for new antimalarial drugs. Several approaches have been adopted in this search including those based on natural products, particularly medicinal plants and herbs. As exemplified in the discovery of quinine and artemisinin, there has been intensified effort in the search of safe and efficacious plant-based antimalarial compounds. This search has yielded moderate success. The current chapter highlights the most promising plant-based drug discovery success with particular emphasis on studies that have reached some advanced clinical stages. With many plant-based compounds exerting antimalarial activities through multiple mechanisms, it is expected that further studies will complement current research efforts towards successful antimalarial drug discovery and development.