Neonatal intensive care units (NICUs) developing a tiny baby program-a clinical approach for care of infants born before 24 weeks' gestation-have a limited, but growing, body of evidence to guide practice. Infants born 22-23 weeks have more immature organ development and physiology than more mature extremely low birth weight infants. Centers of excellence (CoEs) in the care of tiny babies have evolved integrated approaches to clinical care in which the management of each physiologic system impacts other systems. NICUs may find mentorship and potentially better practices from the CoEs, but must apply them with extreme caution in the context of their local practices. In this article, authors from institutions in the process of developing tiny baby programs propose a framework for developing such programs. The authors summarize both operational and physiologic principles that they have found important for consideration.