Abstract—Epigenetics is the study of structurally and functionally relevant molecular changes to the genome that do not constitute a change in the nucleotide sequence such as DNA methylation and histone modifications. These changes are involved in the expression and repression of different genes in a particular cell type. Phorbol esters are diterpene compound known as phorbol 12-myristate 13-acetate (PMA) or Tetradecanoylphorbol-13-acetate (TPA). They are routinely used to study the mechanism of signal transduction in tumor promotion and differentiation induction of different cell types. Recent work on the PMA has linked its function to the epigenetic changes in different cells. This review summarizes the epigenetic changes mediated by PMA and its role in the regulation of gene expression.