The development of resistance to current antibiotic therapies and the use of microorganisms in biological warfare have shown the weaknesses in our arsenal of antibiotic and antiviral drugs. Now, more than ever, the need for novel therapies exists. A major limitation in the development of novel anti-infectives is the identification of an appropriate biochemical target. Our research program focuses on the development of inhibitors for specific targets implicated in the survival of certain human pathogens. We are focused on Mycobacterium tuberculosis, causing TB, Plasmodium falciparum, the major organism causing malaria, and the ESKAPE pathogens. We focus on vulnerabilities in microorganism metabolism that might be targeted by small molecule therapeutic agents. Our work uses structure-guided ligand design, organic synthesis, and biological evaluation to examine these molecules and validate the biochemical target.