In the last several decades, a group of microbial secondary metabolites, the antibiotics, has emerged as one of the most powerful tools for combating diseases. However, thousands of secondary metabolites are known, and they include not only antibiotics but also pigments, toxins, pheromones, enzyme inhibitors, immunomodulating agents, receptor antagonists and agonists, pesticides, antitumor agents, and growth promoters of animals and plants. When appropriate screening has been done on secondary metabolites, numerous drugs outside antibiotics have been found. It seems reasonable from this to conclude that the exploitation of microbial secondary metabolites, useful to man outside antibiotics, has barely been touched. This chapter therefore discusses the principles involved in searching for microorganisms producing metabolites of economic importance, sources of microorganisms used in biotechnology, literature search and culture collection, isolation de novo of organisms producing metabolites of economic importance, strain improvement, selection from naturally occurring variants, and genetic manipulation of the genome of industrial organisms.