Abstract Within the fast-growing field of regenerative medicine stem-cell therapy is well established in various hematologic and immunologic diseases and has received a recent substantial boost from the introduction of gene editing and gene transfer technologies. In neonates, for example, regenerative medicine may benefit those with congenital or acquired disease due to prematurity or perinatal hypoxia-ischemia. We compare and contrast the two main approaches – autologous vs. allogeneic – and summarize the recent advances and applications of interventional stem-cell research in perinatally acquired disorders such as intraventricular hemorrhage, hypoxia-ischemia and stroke. After discussing stem-cell sources and routes of administration, we conclude by highlighting the key opportunities and obstacles in this exciting field.