There is a high demand for new drugs against malaria, which takes millions of 
lives annually. The abuse of classical antimalarials from the late 1940's to the 
early 1980's has bred resistant parasites, which led to the use of more potent 
drugs that ended up by refueling the resistance cycle. An example is 
chloroquine, once highly effective but now virtually useless against malaria. 
Structure-based rational drug design relies on high-resolution target structures 
to allow for screening of selective ligands/inhibitors. For the past two 
decades, and especially after the unveiling of the Plasmodium falciparum genome 
in 2002, enzymes of this lethal malaria parasite species have been increasingly 
attracting the attention of Medicinal Chemists worldwide as promising drug 
targets. There is particular emphasis on proteases having key roles on the 
degradation of host's hemoglobin within the food vacuole of blood-stage 
parasites, as these depend on such process for their survival. Among such 
enzymes, Plasmepsins (aspartic proteases) and, especially, Falcipains (cysteine 
proteases) are highly promising antimalarial drug targets. The present review 
will focus on the computational approaches made so far towards the unraveling of 
the structure, function and inhibition of Falcipains that, by virtue of their 
quite specific features, are excellent targets for highly selective inhibitors.