The development of high-throughput screening and combinatorial chemistry coupled with omic technologies has changed the drug discovery paradigm and the approach for the investigation of target pharmacology. In modern drug discovery, chemical genomics (sometimes called chemogenomics or more generally included as a subset of chemical biology) involves the screening of large chemical libraries (typically combinatorially-derived “druggable” small molecule libraries cover-ing a broad expanse of “diversity space”) against all genes or gene products, such as proteins or other targets (i.e., chemical universe screened against target universe). Drug candidates are expected from the correlations observed during functional analysis of the molecule — gene product interactions. Genomic profiling by the chemical library may also yield relevant new targets and mechanisms. Chemical genomics is expected to be a critical component of drug lead identification and proof of principle determination for selective modulators of complex enzyme systems including proteases, kinases, G-protein coupled receptors, and nuclear receptors.