With recent advances in robotics and high-content screening and analysis methods, transcriptional profiling can now be utilized as a comprehensive forward chemical genomics platform for drug discovery, lead selection and lead optimization. It can be used to define the state of a cell on the basis of gene networks, and to search for drugs that can shift cellular states in a manner predicted at the genome level to be therapeutically beneficial. The treatment of cells with compounds produces transcriptional 'fingerprints' that reveal mechanism-of-action, and enable discrimination between individual compounds based on drug behaviors important to all phases of drug discovery and development.