Lung cancer treatment consists from the basic chemotherapeutic drugs (e.g., platinum analogues) and from pharmaceuticals targeting the different genome of lung tumors (e.g., tyrosine kinase inhibitors). During the last years pharmaceuticals targeting the tumor mutations are approved for first line treatment since they have provided increased overall survival in comparison to standard chemotherapy treatment. Furthermore, due to the increased interest in unrevealing the mechanisms of cell mutation, tumor evolution and tumor cell maintenance the hedgehog pathway has been elicited. Along with Notch and Wnt these three pathways are responsible for progenitor cell development and pulmonary organogenesis. Inhibitors of this pathway have been discovered and their application in the clinical practice is being investigated. However, further understanding of the mechanisms of regulation is needed.