Retroviral vectors offer several potential advantages for attaining persistent expression of a therapeutic gene in airway epithelia for diseases such as cystic fibrosis. However, several problems have limited their application. Developments in vector production and the advent of lentiviral vectors have increased the investigation of recombinant retrovirus for gene transfer to airway epithelia. In addition, an improved understanding of some of the barriers limiting gene transfer has led to increased transduction efficiencies. The development of novel vector formulations and the use of new envelope pseudotypes are examples of recent findings that are leading to advances in this field.