Purpose of Review <p>Perioperative and intraoperative mechanical ventilation is a critical component of anesthesia and surgical management, aimed at maintaining adequate gas exchange and minimizing the risk of perioperative pulmonary complications. While preclinical studies may oversimplify certain aspects, they can also lead to innovative questions by controlling for several confounding factors that cannot be managed in the clinical setting. This narrative review aims to provide a comprehensive overview of insights from experimental studies on perioperative and intraoperative mechanical ventilation.</p> Recent Findings <p>Experimental research applicable to perioperative and intraoperative mechanical ventilation has focused on the interaction between mechanical ventilation and anesthetic agents, the involvement of ventilator-induced diaphragm dysfunction, hemodynamic changes, and innate immune system activation.</p> Summary <p>The translational potential of these experimental findings to clinical practice, current challenges, and future directions in the optimization of perioperative and intraoperative mechanical ventilation are also discussed.</p>