Genetic and epigenetic modifications in DNA contribute to altered gene expression in aging and cancer. In human cancers, epigenetic changes such as DNA methylation, histone modifications, micro RNAs and nucleosome remodelling all control gene expression. The link between the genetics and epigenetics in cancer is further shown by existence of aberrant metabolism and biochemical pathways in cancer or mutation in genes that are epigenetic players. Reversal of these epigenetic changes has been clearly shown to have therapeutic value in various forms of lymphoma and preleukemia and similar results are appearing for the treatment of solid tumors. In this review, we discuss the functional effects of epigenetic changes inducible by hypoxia, the epigenetic alterations in cancer and how they contribute to tumor progression and their relevance to epigenetic therapy.