The application of accurate mass measurement for the determination of elemental formula has its origin in the 1950s and for many years was only carried out using magnetic sector mass spectrometers. The availability of such measurements was limited due to the cost and complexity of the instrumentation and the need for considerable expertise to acquire and interpret the spectra. In recent years the incredible pace of instrumental development has changed this, particularly with the renaissance of time of flight mass spectrometry. This has resulted in instrumentation capable of making accurate mass measurements in a robust fashion becoming available to most practitioners of (mass spectrometry) MS, without some of the earlier technical challenges and at lower cost. In this review the variety of accurate mass measurement instrumentation and techniques and their relative capabilities are discussed, along with a range of applications requiring the determination of elemental formula. © 2005 Wiley Periodicals, Inc.