Lung cancer is the leading cause of cancer related deaths worldwide. The prevalence and frequent deaths associated with lung cancer are due in part to the lack of efficient methods to diagnose the disease progression at an early stage and lack of effective novel treatment strategies. Both genetic and epigenetic mechanisms coordinate in the regulation of transcription which in turn works in regulation of cell growth and proliferation. Numerous genetic and epigenetic changes have been found to be associated with the lung carcinogenesis. The genetic changes include chromosomal abnormalities, oncogene overexpression, mutations in the tumor suppressor genes, changes in DNA repair genes, microsatellite instability, changes in telomerase activity and retrotransposition. These genetic changes either alone or in combination with epigenetic modifications associated with lung cancers such as DNA methylation, histone modifications including histone acetylation and methylation as well as substitution by histone variants have been well studied in lung tumorigenesis. The current review also focuses to address the novel drugs being used in trials such as erlotinib, gefitinib, cetuximab and crizotinib in genetic therapy. Further, a combination of azacitidine, a DNA methyltransferases inhibitor, and entinostat, a histone deacetylases inhibitor, has shown important progress in combined epigenetic therapy against lung tumorigenesis. However, further in depth investigations could identify potential drugs against various types of lung cancer. © 2013 Bentham Science Publishers.