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Since 1961 newborn screening for errors of metabolism (EM) has improved the diagnosis, treatment and outcome of newborns with an EM. Recently, advances in laboratory technology with tandem mass spectrometry (MS/MS) has increased the identification of newborns with an EM. With a single dried filter paper blood spot (Guthrie R, Susi A. A simple phenylalanine method for detecting PKU in large populations of newborn infants. Pediatrics. 1963;32:338-343). MS/MS can identify more than 30 disorders of metabolism This review will explore MS/MS to provide a better understanding of the development and application of this technology to newborn screening for perinatal and neonatal nurses.