The role of anti-human leukocyte antigen (HLA) antibodies in lung transplantation is not fully clear. The presence of pretransplant third-party anti-HLA antibodies or the development of de novo anti-HLA antibodies has been associated with acute posttransplant complications, bronchiolitis obliterans syndrome (BOS), and early mortality in some studies. However, little has been reported regarding the utility of desensitization therapy in sensitized lung transplant recipients. For approximately 3 years, desensitization therapy consisting of intravenous immunoglobulin (IVIG) and, in most instances, extracorporeal immunoadsorption (ECI) has been administered peritransplant to lung transplant recipients at our institution with third-party anti-HLA antibodies or as rescue therapy to those who develop de novo anti-HLA antibodies. Notably, the administration of peritransplant desensitization therapy to these patients has been associated with improvement in several clinical parameters, including acute rejection and BOS. Furthermore, administration of rescue IVIG with or without ECI has been associated with an overall improvement in the rate of pulmonary function decline. Our experience suggests that desensitization therapy may be beneficial for lung transplant recipients with pretransplant or de novo anti-HLA antibodies. We discuss the appropriateness and clinical impact of IVIG and ECI in sensitized lung transplant recipients as well as cellular mechanisms that may contribute.