Lung transplantation is now a viable therapeutic option in the care of patients with advanced pulmonary parenchymal or pulmonary vascular disease. Lung transplantation, however, with chronic posttransplant immunosuppression, creates a uniquely vulnerable population of patients likely to experience significant life-threatening complications requiring intensive care. The introduction of several novel immunosuppressive agents, such as sirolimus and mycophenolate mofetil, in conjunction with more established agents such as cyclosporine and tacrolimus, has greatly increased treatment options for lung transplant recipients and likely contributed to improved short-term transplant outcomes. Modern transplant immunosuppression, however, is associated with a host of complications such as opportunistic infections, renal failure, and thrombotic thrombocytopenic purpura. The main focus of this review is to provide a comprehensive summary of modern immunotherapy in lung transplantation and to increase awareness of the serious and potentially life-threatening complications of these medications.