The study of antibiotics and other fermentation products has shown that a seemingly unlimited number of compounds with diverse structures are produced by microorganisms. The continued high rate of discovery of new chemical entities, in the light of the abundance of microbial products already described, is due to creative screening procedures that incorporate such features as the emphasis on unusual microorgnaisms, their special propagation and fermentation requirements, supersensitive and highly selective assays, genetic engineering both for the biosynthesis of new compounds and in the development of screening systems, early in vivo evaluation, improved isolation techniques, modern procedures for structure determination, computer-assisted identification, and an efficient multidisciplinary approach. This review focuses on the genesis and development of the gamut of methodologies that have led to the successful detection of the wide variety of novel secondary metabolites that include antibacterial, antigungal, antiviral and antitumour antibiotics, enzyme inhibitors, pharmacologically and immunologically active agents, products useful in agriculture and animal husbandry, microbial regulators, and other compounds for which no bioactive role has yet been found.