AIM: The neonatal intensive care unit (NICU) provides life-saving medical care for an increasing number of newborn infants each year. NICU care, while lifesaving, does have attendant consequences which can include repeated activation of the stress response and reduced maternal interaction, with possible negative long-term impacts on brain development. Here we present a neuroscientific framework for considering the impact of music on neurodevelopment in the NICU of infants born preterm and evaluate current literature on the use of music with this population to determine what is most reliably known of the physiological effects of music interventions. METHOD: Using online academic databases we collected relevant, experimental studies aimed at determining effects of music listening in infants in the NICU. These articles were evaluated for methodological rigor, ranking the 10 most experimentally stringent as a representative sample. RESULTS: The selected literature seems to indicate that effects are present on the cardio-pulmonary system and behavior of neonates, although the relative effect size remains unclear. INTERPRETATION: These findings indicate a need for more standardized longitudinal studies aimed at determining not only whether NICU music exposure has beneficial effects on the cardio-pulmonary system, but also on the hypothalamic-pituitary-adrenal axis, brain structures, and cognitive behavioral status of these children as well. WHAT THIS PAPER ADDS: Provides a neuroscience framework for considering how music might attenuate stress in neonatal intensive care unit (NICU) infants. Considers how repeated stress may cause negative neurodevelopmental impacts in infants born preterm. Posits epigenetics can serve as a mechanistic pathway for music moderating the stress response.