Extracorporeal membrane oxygenation (ECMO) is an important rescue strategy for neonates with severe cardiorespiratory failure, yet its role in the management of hypoxic–ischemic encephalopathy (HIE) remains subject to debate. Historically, clinicians have been reluctant to offer ECMO to infants with significant neurological injury because of concerns related to poor neurodevelopmental outcomes and elevated risk of complications such as hemorrhage and stroke. Over the past two decades, however, accumulating evidence has suggested that many neonates with HIE not only tolerate ECMO well but may also achieve meaningful survival and functional recovery. In this state-of-the-art narrative review, we surveyed and synthesized observational studies, retrospective cohorts, and case series published since 2000 that evaluated ECMO in neonates with HIE. While randomized controlled trials dedicated exclusively to this population remain scarce, the available data indicate that ECMO can be safely implemented alongside standard therapies—including therapeutic hypothermia—without uniformly prohibitive rates of bleeding or adverse neurodevelopment. Although small sample sizes and single-center experiences limit the strength of these conclusions, survival rates in combined TH-ECMO cohorts are often reported above 80 to 90%, with a substantial proportion of survivors demonstrating acceptable early neurodevelopmental outcomes. Overall, the growing clinical acceptance of ECMO in HIE highlights the need for careful, individualized assessment of benefits and risks, as well as transparent discussions with families. Future multicenter collaborations focusing on robust longitudinal follow-up and evidence-based protocols will be essential to guide best practices and optimize outcomes for this high-risk neonatal population.