Leishmaniasis is one of the neglected tropical diseases (NTDs), mainly affecting impoverished communities and having varied ranges of pathogenicity according to the diverse spectrum of clinical manifestations. It is endemic in many countries and poses major challenges to healthcare systems in developing countries. Despite the fact that most of the current mono and combination therapies are found to be failures, clear perception of gene essentiality for parasite survival are now desideratum to identify potential biochemical targets through selection. Here we used the metabolic network of L. major, to perform a comprehensive set of in silico deletion mutants and have systematically recognized a clearly defined set of essential proteins by combining several essential criteria. In this paper we summarize the efforts to prioritize potential drug targets up to a five-fold enrichment compared with a random selection.