Several pathways of carbon metabolism, or parts of them, play important roles in the proliferation and virulence of the human pathogenic stage of Leishmania, the intracellular amastigotes. Kinetic and structural properties of a considerable number of enzymes from this metabolic network from Leishmania spp. and/or related Trypanosoma spp. have been studied in detail and compared with the enzymes catalysing the corresponding reactions in human. This has allowed the identification of parasite-enzyme-specific features. Potent and selective inhibitors of the trypanosomatid enzymes have been developed to exploit these unique properties. Some of these compounds stunt the proliferation of parasites, including the intracellular Leishmania amastigotes, without affecting growth of host cell lines, and/or affect their virulence in infected animal models.