Epigenetic modifications at the DNA level play a central role in establishing the chromatin state and thereby influencing biological function. Several disorders arise from aberrant epigenetic patterns on DNA, cancer being widely explored as an epigenetic disorder. In fact several cancers are associated with a hypermethylator phenotype, which essentially functions as a ‘driver’ of tumorigenesis. Aberrant DNA methylation patterns arise from disrupting the ‘writers’ or ‘erasers’ of the DNA methylation pathway, coordinately functioning to regulate DNA epigenetic marks. Cancer associated deregulatory mechanisms targeting functional disruption of the molecular components of the DNA methylation pathway, and their contribution to cancer initiation and progression are being increasingly appreciated. Understanding these mechanisms of deregulation is central to identifying new targets for therapeutic intervention, in both cancer prevention and treatment.