Since its inception, Extracorporeal Membrane Oxygenation (ECMO) and its application have significantly evolved in the face of numerous challenges and clinical needs. Here, we trace the historical evolution, challenges, and recent advancements in Extracorporeal Membrane Oxygenation (ECMO), highlighting milestones, like the “Bubble Oxygenator” and the standardization efforts by the Extracorporeal Life Support Organization (ELSO). Technological innovations, including miniaturization and enhanced oxygenators, have rendered ECMO more portable and efficient. Global applications, like managing epidemics and supporting developing countries, are discussed, along with the transformative impact of telemedicine on ECMO care. In summary, this chapter illuminates ECMO’s journey from its historical origins to its transformative modern role. It underscores its adaptability and pivotal position in the field of medical science and patient care.