The principles of selective ion monitoring are described. Choice of instrumentations, derivatives, and internal standards is discussed. The most important factors influencing sensitivity, specificity, and precision are summarized. Applications of selective ion monitoring for quantitative assay of steroids, fat soluble vitamins, triglycerides, prostaglandins, biogenic amines, amino acids, carbohydrates, and several other organic compounds of clinical interest are critically reviewed. It is concluded that isotope dilution selective ion monitoring is one of the most sensitive and accurate techniques presently available for quantitation of a large number of endogenous compounds of clinical interest. In view of the high accuracy, the technique is useful not only for the clinical chemists dealing with determination of specific compounds which are difficult to analyze by other methods, but also for those dealing with quality control of routine analyses of simple organic compounds.