In neonatal care, decisions are made on behalf of newborn infants by their parents or, in some instances, health professionals. This paper examines how the best interest standard is the most appropriate focus for decision-making concerning neonates. The components of surrogate decision-making are discussed from the perspective of the neonate's interests and the contribution of the various persons involved in caring for neonates. An argument is presented for the use of best interests when making decisions and the interpretation of best interests is explored. By examining the ethical approaches using best interests, an argument is put forward for caring as an expression of best interests. How some nurses use the best interest standard in their practice is described. The unique perspective nurses may have because of their philosophy, circumstances, experience and concern for neonates is discussed. Examples are used from the literature to support the argument for nurses being in roles and relationships where the neonate's interests are the basis of practice. How nurses classify infants on the basis of their future outcome is used to illustrate how nurses can apply the best interest standard. Ethical approaches of care and cure are used to show the best interest standard as applied to neonates. Caring as an expression of best interests is recommended for nursing decisions and actions using infant outcomes as a focus for caring and best interests.