Utilizing biology of PD-1: PD-L1 interaction related pathways for cancer immunotherapy is an emerging concept in cancer research. However, there is limited literature on epigenetic regulation of PD1 gene (PDCD1). Promising data from clinical trials of PD/PDl-1 immunotherapy in melanoma, renal cancers, colorectal and lung cancers has generated a lot of hope for successful treatment of patients. Immunotherapy in cancers has a significant role in strategizing NCI’s Cancer Moonshot Program of US NIH and FDA policies. The cost of the treatment by immunotherapy is extremely high. This preview presents a concise compilation of current knowledge on how the PD-1 gene is regulated in different cancers and infections. We have also discussed about epigenetic regulation of PDCD1 gene, especially the effect of different epigenetic inhibitors of DNA methylation and histone modifications at different steps in PD-1 regulation.