Lung transplantation currently stands as the only therapeutic option that carries the potential to restore patients with advanced cystic fibrosis to a more normal state of health. Nonetheless, the procedure carries significant risk and median survival following transplantation is only 5 years. This article discusses the currently achievable outcomes and the common short-comings of transplantation. Strategies to optimize outcomes through appropriate patient selection, use of living donors, and novel research initiatives are discussed.