Malaria has killed more people throughout our history than any other cause, yet finding a way to defeat this parasitic infection remains a serious problem. Now, François Diederich of the Swiss Federal Institute of Technology in Zurich and colleagues at the University of Victoria, Canada, Washington University, St. Louis, USA, and Actelion Pharmaceuticals in Switzerland are focusing their attention on a new pharmaceutical target through which to attack the malaria parasite Plasmodium falciparum. The target is a group of enzymes known as plasmepsins, which belong to the family of aspartic protease enzymes. These enzymes dismantle human hemoglobin to release the amino acids plasmodia need to grow. Computer modeling of the plasmepsin II active site has led to a new group of enzyme inhibitors, which the team is currently optimizing for efficacy. Human proteases are fortunately unaffected, which bodes well for avoiding side-effects.