The practice of lung transplantation is constrained by a shortage of suitable donor organs. Furthermore, even "optimal" donor lung grafts are at risk of significant dysfunction perioperatively. Significant insights into the cellular and molecular mechanisms of pulmonary ischemia-reperfusion injury have occurred since the publication of previous reviews on lung preservation 3 to 4 years ago. Recent evidence indicates that the endothelium plays an essential role in regulating the dynamic interaction between pulmonary vasodilatation and vasoconstriction and is a major target during lung injury. In addition, the composition, function, and metabolism of pulmonary surfactant produced by alveolar type II cells are increasingly being recognized as important factors in pulmonary ischemia-reperfusion injury. We hypothesize that reperfusion after a period of pulmonary ischemia results in significant endothelial and alveolar type II cell dysfunction and that an important strategy in lung preservation is to preserve the integrity of these cells in the face of this injury. Given the persistent shortage of lungs available for transplantation, laboratory studies need to focus also on the "rescue" of compromised donor lungs that would have been previously regarded as unsuitable. Importantly, innovative work from the laboratory needs to be translated into clinical practice via prospective, randomized trials to ensure that the prevalence of postoperative lung graft dysfunction is reduced and the shortage of lung grafts for transplantation is alleviated.