In the first part of this account, the antimalarial drug artemisinin is presented, and the current hypotheses on the mechanism of action of this endoperoxide-based drug are reviewed. The alkylating ability of artemisinin and synthetic analogues toward heme related to their antimalarial efficacy are underlined. Some possible ways for discovery of new drugs, especially the design of trioxaquines, new active molecules recently patented that have been prepared by covalent attachment of a trioxane residue having alkylating ability to a quinoline moiety known to easily penetrate within infected erythrocytes, are presented.