Lung cancer is the largest and the most common cause of cancer-related deaths worldwide. The cure rate for lung cancer remains lowest among all malignancies. The discovery of new chemical agents with activity in first onset and recurrent disease is crucial for advancing treatment of patients with pulmonary tumors. Camptothecins are known as inhibitors of topoisomerase I, one of the key enzymes for DNA replication and subsequent cell proliferation. Preclinical and clinical studies had shown that the camptothecins are active against lung cancer and other solid malignancies. In this paper, we review the status of camptothecin and derivatives for treatment of pulmonary cancers, including the development of new formulations and, particularly, novel aerosol routes of drug administration, and their application in combination therapy.