Book excerpt: Malaria is a threat to mankind and responsible for millions of cases of morbidity and mortality worldwide. Plasmodium parasite is responsible for causing disease. This work investigates and reveals the hidden information inside the parasite genomes using comparative genome analysis and codon usage bias study. The possibility of using variable surface proteins as a common drug target has been checked in both the human infecting Plasmodium species and it was found that variable surface proteins cannot be used as a common drug target due to existence of sequential and structural differences at both the genome and proteome level. Metabolic network information is also utilized in this piece of work for identifying new drug targets. Further in silico approaches viz. molecular modeling, structure-based 3D pharmacophore model generation, virtual screening and docking etc. were also utilized to find the drug prototypes.