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The clinical application of blood gas analysis and pulse oximetry is regulated in the United States, with new guidelines enforcing the use of these technologies to monitor the baby in the delivery room and special care nursery. To date, the practice of delivery room resuscitation of the newborn in the United States has varied widely, with pulse oximetry gaining in popularity. However, the data used by the manufacturers of these technologies relies on test reagents, adult data, and controlled environments; indeed, every effort is taken by these technology manufacturers to isolate and limit variables in order to develop steady-state conditions during which reference data is collected. Unfortunately, the environs of caring for the sick newborn and physiological aspects unique to the infant make for circumstances less conducive to accurate data acquisition. To that point, a recent report of clinical use found the accuracy of pulse oximetry SpO 2 values in neonates was appreciably worse than manufacturers’ claims. In this issue, we review the current literature describing how manufacturers establish instrument accuracy, examine factors that can degrade accuracy, and provide tools for maximizing blood gas analysis and pulse oximetry performance in neonatal care.