Extracorporeal membrane oxygenation (ECMO) traditionally has been used under deep sedation and mechanical ventilation. However, recent advancements have led to the development of awake ECMO strategies, allowing patients to remain conscious. This comprehensive review explores the evolving landscape of awake ECMO, from its historical context to current practices and future directions. We examine the rationale behind awake ECMO, including potential benefits such as preserved muscle strength, reduced sedation-related complications, and improved patient engagement in care. The review details key considerations in patient selection, emphasizing the importance of careful physiologic, psychological, and social assessment to identify suitable candidates for awake ECMO. Technical aspects of awake ECMO implementation are discussed, including cannulation strategies, circuit management, and the integration of extracorporeal support with spontaneous breathing. The unique challenges in managing awake ECMO patients are highlighted, addressing issues such as pain control, anxiety management, and early mobilization protocols. The review synthesizes current evidence on outcomes associated with awake ECMO, focusing in particular on its application as a bridge to lung transplantation and in acute respiratory failure. Although early data suggest promising results in selected populations, the need remains for more robust, large-scale studies to definitively establish the efficacy and safety of awake ECMO across various clinical scenarios. Emerging technologies and future directions in awake ECMO are explored, including the development of more compact and portable systems, advanced monitoring tools, and novel approaches to patient–ECMO interaction. Finally, the importance of specialized training programs and the potential for dedicated awake ECMO units within specialized centers are examined.