The lung represents an attractive target organ for somatic gene therapy strategy in that, (1) it is easily accessible by vectors, (2) most frequent hereditary disorders, cystic fibrosis (CF) and alpha1-antitrypsin deficiency (alpha1AT), occur in the lung, and (3) carcinoma of the lung is apparently a most common cause of death in humans. To date, approximately 400 clinical protocols for human gene therapy have been approved, and approximately 10% of the protocols target lung diseases such as cystic fibrosis (CF) and lung cancer. Currently available data from some of these human trials have successfully demonstrated that gene transfer to the human lung is possible, and that the strategy of overexpressing exogenous genes for curing or controlling lung diseases is potentially promising. In this manuscript, focusing on gene therapy of lung disorders, we aim to give an overview of the hurdles of current gene transfer strategies to overcome, then and also we aim to review recent, remarkable progresses in the vector biology that are potentially promising to maximize safety and efficiency of gene therapy. In addition, based on the most recent advances in the understanding of the molecular biological aspects of the pathogenesis of lung cancer, asthma, pulmonary fibrosis, and acute lung injury, novel therapeutic strategies of gene therapy for inflammatory and malignant diseases of the lung are discussed.