Music-based intervention for hospitalized newborn infants has traditionally been based in a biomedical model, with physiological stability as the prime objective. More recent applications are grounded in other theories, including attachment, trauma and neurological models in which infant, parent and the dyadic interaction may be viewed as a dynamic system bound by the common context of the neonatal intensive care unit (NICU). The immature state of the preterm infant's auditory processing system requires a careful and individualized approach for the introduction of purposeful auditory experience intended to support development. The infant's experience of an unpredictable auditory environment is further compromised by a potential lack of meaningful auditory stimulation. Parents often feel disconnected from their own capacities to nurture their infant with potentially life-long implications for the infant's neurobehavioral and psychological well-being. This perspectives paper will outline some neurological considerations for auditory processing in the premature infant to frame a premise for music-based interventions. A hypothetical clinical case will illustrate the application of music by a music therapist with an infant and family in NICU.