Mass spectrometry (MS) has had an important place in clinical chemistry and laboratory diagnostics for the past 4 decades. Historically, the value of MS was in its ability to measure the mass of bioactive metabolites (eg, amino acids, fatty acids, organic acids, steroids, lipids, neurotransmitters) in a selective, accurate, and comprehensive manner. Its primary use during this period was the organic acid analysis of urine for the diagnosis of metabolic abnormalities, and this capability remains one of its most important applications. Traditionally, most of these MS analyses were conducted in specialty, expert laboratories because the complex profiles produced by such devices required interpretation by experts in intermediary metabolism. In these applications, a mass spectrometer was often used in conjunction with a physical separation device (eg, gas chromatograph) to detect the mass of the intact molecule and its fragments. The fragmentation pattern uniquely identified a particular molecule that, when coupled to a retention time on a chromatographic device, was considered the gold standard in clinical analysis.