Primary graft dysfunction is a form of acute injury after lung transplantation that is associated with significant short- and long-term morbidity and mortality. Multiple mechanisms contribute to the pathogenesis of primary graft dysfunction, including ischemia reperfusion injury, epithelial cell death, endothelial cell dysfunction, innate immune activation, oxidative stress, and release of inflammatory cytokines and chemokines. This article reviews the epidemiology, pathogenesis, risk factors, prevention, and treatment of primary graft dysfunction.