Clinical microbiology is in the midst of a new era. Methodology that is based on nucleic acid detection has slowly appeared in the diagnostic laboratory, and is revolutionizing our ability to assist physicians in the diagnosis and management of patients suffering from infectious diseases. Much like the introduction of immunoassays built around hybridoma technology in the 1980s, considerable doubt and promise exist hand in hand in the 1990s. Conventional testing that is technically straight forward, informative, and timely will always be a part of clinical microbiology; however, considerable room for improvement exists with organisms/diseases for which laboratory methods are limited. Nucleic acid methodology will have its greatest and long-awaited impact in this arena.