Over 50 years ago, visionary researchers began work on an extracorporeal artificial placenta to support premature infants. Despite rudimentary technology and incomplete understanding of fetal physiology, these pioneering scientists laid the foundation for future work. The research was episodic, as medical advances improved outcomes of premature infants and extracorporeal life support (ECLS) was introduced for the treatment of term and near-term infants with respiratory or cardiac failure. Despite ongoing medical advances, extremely premature infants continue to suffer a disproportionate burden of mortality and morbidity due to organ immaturity and unintended iatrogenic consequences of medical treatment. With advancing technology and innovative approaches, there has been a resurgence of interest in developing an artificial placenta to further diminish the mortality and morbidity of prematurity. Two related but distinct platforms have emerged to support premature infants by recreating fetal physiology: a system based on arteriovenous (AV) ECLS and one based on veno-venous (VV) ECLS. The AV-ECLS approach utilizes only the umbilical vessels for cannulation. It requires immediate transition of the infant at the time of birth to a fluid-filled artificial womb to prevent umbilical vessel spasm and avoid gas ventilation. In contradistinction, the VV-ECLS approach utilizes the umbilical vein and the internal jugular vein. It would be applied after birth to infants failing maximal medical therapy or preemptively if risk stratified for high mortality and morbidity. Animal studies are promising, demonstrating prolonged support and ongoing organ development in both systems. The milestones for clinical translation are currently being evaluated.