Epigenetic modulation can affect the characteristics of cancers. Because it is likely to manipulate epigenetic genes, they can be considered as potential targets for cancer treatment. In this comprehensive study, epigenetic drugs are categorized according to anticancer mechanisms and phase of therapy. The relevant articles or databases were searched for epigenetic approaches to cancer therapy. Epigenetic drugs are divided according to their mechanisms and clinical phases that have been approved by the FDA or are undergoing evaluation phases. DNA methylation agents, chromatin remodelers specially HDACs, and noncoding RNAs especially microRNAs are the main epi-drugs for cancer. Despite many challenges, combination therapy using epi-drugs and routine therapies such as chemotherapy in various approaches have exhibited beneficial effects compared with each treatment alone. Cancer stem cell targeting and epigenetic editing have been confirmed as definitive pathways for cancer treatment. This paper reviewed the available epigenetic approaches to cancer therapy.