Interferons (IFNs) are a family of cytokine mediators that are critically involved in alerting the cellular immune system to viral infections of host cells. There are three major classes of IFNs, as follows: IFN-alpha; IFN-beta; and IFN-gamma. IFNs are being investigated and applied in various respiratory disorders, including interstitial lung diseases, lung cancer, malignant mesothelioma, malignant pleural effusions, and respiratory infections. Recent promising preliminary results concerning patients with idiopathic pulmonary fibrosis who have been treated with IFN-gamma1b should prompt the performance of further confirmatory well-designed multicenter trials. IFN-gamma is emerging as an important cytokine for use in the treatment of patients with infectious diseases, including multidrug-resistant pulmonary TB. A better understanding of IFN biology, indications, side effect profiles, and toxicity management will aid in optimizing its use in the treatment of patients. The purpose of this article is, therefore, to review the current clinical use of IFNs in the treatment of patients with respiratory diseases.