Since the market for antiparasitic drugs is in poor Third World countries, innovative and cost effective approaches to antiparasite drug discovery and development are urgently needed. Development of broadspectrum antiprotozoal agents acting against multiple protozoan parasites offers numerous advantages in addressing the challenges inherent in the aforementioned approaches. With a view to addressing these challenges, our research group at the University of Cape Town has initiated research projects whose main objectives include: (i) the development of single agents that provide target-directed inhibition of multiple protozoans; (ii) the development of single agents that provide maximal antiprotozoan activity by acting against multiple parasitic targets. The human diseases of leishmaniasis, malaria and trypanosomiasis have been selected for proof of concept studies with cysteine proteases and oxidoreductases present in the respective parasites selected as enzyme targets for antileishmanial, antimalarial and antitrypanosomal drug discovery efforts.