Various features of the evolution of a few antimalarial drugs including amodiaquine, dihydrofolate-reductase inhibitors, and artemisinin are described. The mechanism of action of artemisinin is detailed to explain the information of the main metabolites and drug design of certain compounds. Structure-activity and structure-neurotoxicity relations are reported. A few examples of cyclic peroxycetal synthesis are given. Finally, trends in new and novel compounds are presented.