Malaria remains a devastating disease in the developing world with nearly a half billion people infected each year by the bite of a mosquito that carries the parasite, Plasmodium falciparum, which causes the disease. There is a desperate need to develop new compounds to combat malaria as the parasite has developed resistance against the classic drugs primaquine and chloroquine. The proteolytic enzymes of the parasite have been identified as potential targets for drug discovery due to the known requirement of the digestion of hemoglobin in the parasite digestive vacuole. Among the proteolytic enzymes found in P. falciparum, the aspartic proteinases, known as plasmepsins, are discussed in this chapter. The completion of the sequencing of the genome of P. falciparum revealed a total of ten enzymes in the aspartic proteinase class, with seven of these being found in the stage of the parasite that can be found in the erythrocyte of infected humans. The current information on these seven enzymes is presented and the possibility of identifying one or more key enzymes as targets for drug discovery is discussed.