Cystic fibrosis (CF) is characterized by accumulation of thick mucus in the lungs and is associated with a high incidence of bacterial infection. Mutations in the gene encoding CF transmembrane conductance regulator (CFTR) underlie the disease. Gene therapy to deliver a normal copy of the CFTR gene has shown promise in both pre-clinical models and clinical trials; however, current gene delivery methods are inefficient and do not result in sustained expression of functional CFTR in the airways. Two studies in this issue of JCI Insight report the development and use of viral vector-based delivery of CFTR in pig models of CF. A team led by Patrick Sinn and Paul McCray Jr. of the University of Iowa developed a lentiviral-based vector that was delivered through the nose to newborn CF pigs. Analysis of these animals revealed evidence of functional CFTR expression in the airways. A second team led by Joseph Zabner of the University of Iowa and David Schaffer of the University of California, Berkeley, generated an adeno-associated virus (AAV) that homes to the pig airway to mediate expression of functional CFTR in the airways of 1 week-old CF pigs. Together, these reports indicate that viral vector-based approaches could potentially improve the effectiveness of CFTR gene therapy.