Mass spectrometry (MS) is rapidly transitioning from specialized clinical testing— drugs of abuse confirmations, newborn screening, and steroid analysis— to being broadly applied throughout clinical laboratory medicine. A special January issue of Clinical Chemistry was dedicated to exploring current uses of MS in clinical laboratories, challenges to employing the technology, and emerging areas of potential advancement. Interest in MS is driven by its analytical specificity and sensitivity. In clinical laboratories, MS is being used for detection of small molecules (biogenic amines, amino acids, and organic acids) and larger compounds (proteins and ribosomal RNA). Its use has penetrated most areas of laboratory medicine including microbiology, anatomic pathology, genetic disorders and pharmacogenetics, immunology, endocrinology, and toxicology. Despite the widening adoption of clinical MS, real challenges remain to expanded application. Among the areas experts say that improvements can be made are: increasing ease of use, including, cutting sample prep and better connectivity to automation and laboratory information systems/laboratory information management systems; bringing down the high capital cost of equipment ($200,000 to $500,000); addressing lack of automation which necessitates a skilled labor force (especially for design and validation of laboratory-developed tests); and resolving regulatory uncertainty. In addition to the general regulatory uncertainty around laboratory-developed […]