Lung transplantation has emerged as a viable option for the treatment of end-stage disease attributable to a wide spectrum of primary disorders. Although many aspects of patient management are indifferent to the underlying indication, important differences related to timing of transplantation, selection of candidates, choice of procedure, and post-transplant complications exist among the various primary disease groups. Optimal utilization of transplantation for these challenging patient populations with advanced lung disease mandates a thorough appreciation of those differences.