Organized search for microbial metabolites of pharmaceutical and clinical importance began in the late 1960s when methods were developed for the isolation of enzyme inhibitors of microbial origin. This led to the discovery of many drugs of clinical importance. One such enzyme inhibitor is a beta-lactamase inhibitor which is administered with beta-lactam antibiotics; the other is an inhibitor of cholesterol accumulation, while a third is the immunosupressant, cyclosporin A. Anti-microbial and anti-tumor agents produced by microorganisms were discussed in another chapter; and this chapter focuses on other products with pharmaceutical relevance outside antibiotics. It presents conventional methods for assaying microbial metabolites as a means of discovering those with positive bioactive activities with the potential of resulting in new drugs; as well as newer methods which have come into being following the recent successes with the human genome project and such developments as the involvement of the computer in biotechnology, or bioinformatics. Specific topics are cell-based assays, receptor binding assays, enzyme assays, computer aided drug design, genomic methods including unculturable microorganisms and processes for approval of drugs and post approval research.