In 1972 Yellow Springs Instrument Co., Inc. (YSI) introduced the first commercial instrument which could measure glucose in diluted whole blood by use of an enzyme-based biosensor. Until 1986 YSI had a monopoly of this technology for clinical chemistry. Since 1986 another ten companies have commercialized the technology. Enzyme-based biosensors for clinical chemistry are now available for glucose, lactate, and urea. Until 1975 the annual number of papers on enzyme-based biosensors is sparse, but from then there is a significant increase in the number of publications. The commercial interest in glucose is reflected in the number of patents covering this analyte: close to fifty per cent of the patents cover this type of sensor while less than ten per cent of the scientific papers are on glucose sensors. The major problems in developing enzyme-based biosensors for clinical chemistry have been achievement of the necessary linear range and elimination of interferences from the blood. The slow penetration of enzyme-based biosensors into clinical chemistry analysis is due to the fact that it is difficult to develop sensors which meet the high accuracy and reliability requirements, are manufacturable, and have an acceptable shelf life. The number of commercial products utilizing enzyme-based biosensors will probably remain limited in the future due to the limited number of analytes for which a suitable enzyme exists, and for which the use of an enzyme-based biosensor offers the advantages that can justify the costs of development.