The role of intraoperative mechanical support during lung transplantation (LTx) is essential to provide a safe hemodynamic and ventilatory status during critical intraoperative events. This hemodynamic and ventilatory stability is vital to minimize the odds of suboptimal outcomes, especially considering that, due to the scarcity of donors and the fact that more and more patients with significant comorbidities are being considered for this therapy, a more aggressive approach is often needed by the transplant centers. Hence, the attenuation of any potential injury that can happen during this complex event is paramount. While a thorough assessment of the donor and optimization of postoperative care is pursued, certainly protective intraoperative management would also contribute to better outcomes. Understanding each patient’s underlying anatomy and cardiopulmonary physiology, associated with awareness of critical events during a complicated procedure like LTx, is essential for a precise indication and safe use of support. Cardiopulmonary bypass (CPB) and veno-arterial extracorporeal membrane oxygenation (VA ECMO) have been the most common approaches used, with the latter gaining popularity more recently and we have used VA ECMO exclusively for the last decade. New technologies certainly contributed to more liberal use of VA ECMO intraoperatively, enabling a protecting and physiologic environment for the newly implanted grafts. In this setting, potential prophylactic use for lung protection during a critical period is also considered.