The provision of quality end-of-life care is essential when a neonate is dying. End-of-life care delivered in a neonatal intensive care unit (NICU) must consider the needs of both the newborn and their family. The purpose of this paper is to demonstrate how comfort theory and its associated taxonomic structure can be used as a conceptual framework for nurses and midwives providing end-of-life care to neonates and their families. Comfort theory and its taxonomic structure are presented and issues related to end-of-life care in the NICU are highlighted. A case study is used to illustrate the application of comfort theory and issues related to implementation are discussed. The delivery of end-of-life care in the NICU can be improved through the application of comfort.