Cancer has been traditionally regarded as a disease caused by genetic mutations. However, since the development of epigenetic and our better understanding of cancer itself, scientists now recognize the role of epigenetic factors in cancer. Cancer metastasis, the spread of cancer cell to secondary sites, is one of the most dangerous events in late cancer stages. With no exception, epigenetic factors also play important roles in cancer metastasis as they do in other cancer events. E-cadherin gene has been identified as the key regulator of metastasis and is under the control of a series of epigenetic factors. By summarizing results of epigenetic regulation of E-cadherin gene and other potential genes involved in metastasis, I wish to propose a model that multiple epigenetic factors work together to control metastasis. Also, some current therapies targeting epigenetic regulations are reviewed and potential therapeutic strategies are raised.