The widespread resistance of Plasmodium to existing antimalarials generates an urgent need to develop new antimalarial drugs. A crucial component of the protein translation machinery, the aminoacyl-tRNA synthetases, has been validated as promising antimalarial targets. We focus on one member of this family, methionyl-tRNA synthetase, which has been identified as potential drug target in both eukaryotic and prokaryotic pathogens including Trypanosoma brucei, Clostridium difficile and Staphylococcus aureus. There are two versions of MetRS in Plasmodium falciparum, one of them has a N-terminal bipartite leader sequence and is expected to be apicoplast targeted while the other version lacks obvious targeting sequences and is expected to be cytosolic. We have generated HA-tagged recombinants to study localisation and expression of these proteins in P. falciparum. A recombinant HIS-tagged PfMetRS was overexpressed in E.coli and purified and will be used for structural characterisation, and for activity and inhibitor assays. We are seeking novel inhibitors of the Plasmodium MetRS enzymes using in silico docking approaches, as well as testing analogues of known inhibitors of bacterial MetRSs. Several of these compounds kill P. falciparum grown in culture, and experiments to establish the targets of these compounds are underway.