Gene therapy to replace the defective cystic fibrosis transmembrane conductance regulator (CFTR) is a potential strategy for treating cystic fibrosis. However, gene transfer to airway epithelial cells by current gene therapy vectors is inefficient, making the clinical benefit of such an approach unlikely. Now on page 970, Alton and colleagues decribe a Sendai virus (SeV) vector that boosts transfection efficiency by several log orders over cationic liposomes or adenovirus, to levels compatible with therapeutic application. They achieved high levels of reporter gene transfer to lungs of mice and ferrets. Gene transfer was mediated by the sialic acid receptor, which is present on most cell types, including the apical side of the conducting airways. Based on this study, the SeV vector appears to posess important advantages for gene transfer to airway epithelium: its uptake is not inhibited by mucus, and it mediates gene transfer to the cytoplasm where exogenous gene expression occurs, removing the barrier of nuclear import.