Lung carcinogenesis is a complex process requiring the acquisition of genetic mutations that confer the malignant phenotype as well as epigenetic alterations that may be both manipulated in the course of therapy. Aberrant gene function and transcriptional silencing by CpG island hypermethylation has become a critical component in the initiation and progression of lung cancer. Growing evidence shows that acquired epigenetic abnormalities participate with genetic alterations to cause this dysregulation. Human and animal studies have fostered significant advances in elucidating the role of gene-specific methylation in cancer initiation and progression, the modulation of DNA methylation by carcinogen exposure and the ability of pharmacologic agents to reverse promoter hypermethylation, making it an attractive target to pursue for prevention of lung cancer. This review focuses on how lung cancer predisposing factors participate in epigenetic alterations of lung neoplasia, and discusses the growing implications of these alterations for strategies to control cancer.