The application of molecular biology to microbiology has led to a. surge of new information about most infectious microorganisms, the pathogenesis of the infections they cause, and the specific microbial antigens involved in the immune response to these infections. The simultaneous application of the same techniques to diagnosis and epidemiology has also shown great promise, but these developments have not yet had a major effect on the routine practice of medicine. For some purposes, direct probe tests perform as well as other available methods. However, for most infections, these methods have not been proven sufficiently sensitive. The latest generation of highly sensitive diagnostics based on the polymerase chain reaction will overcome this technical obstacle and may revolutionize the management of many infections. Difficulties inherent in performing these tests will require special procedures and training in clinical laboratories to ensure that they are performed reliably. Nucleic acid-based methods for epidemiologic typing of microorganisms and for identification of noncultivatable pathogens are particularly useful for analysis of poorly cultivatable, dangerous, or otherwise untypeable microorganisms.