Gene therapy is the treatment of any disorder or pathophysiologic state based upon the transfer of genetic information. The lung represents a major target of gene therapy for the treatment of genetic disorders such as cystic fibrosis and alpha 1-antitrypsin deficiency. Other diseases are also being targeted, including pulmonary inflammation, surfactant deficiency, pulmonary hypertension, lung cancer, and malignant mesothelioma. This review will examine some general concepts regarding gene transfer and gene therapy, provide an overview of the current vectors being developed to achieve safe and efficient gene transfer, and summarize the ongoing work to apply this new technology to the treatment of both inherited and acquired pulmonary diseases. Although tremendous progress has been made in the ability to successfully transfer genes to cells, there are several unresolved problems limiting the clinical application of this technology to human pulmonary disease. However, as vector technology evolves, gene therapy may become a reality for a number of lung diseases.