Recent advances in cancer research showed that changes of the cell "epigenome" contribute significantly to the development and progression of cancer. Similar to genetic alterations, epigenetic modifications can be transmitted to the next generation and used to turn off and/or on certain genes or pathways that may confer survival benefit to a malignant cell. However, epigenetic changes are readily reversible raising the possibility of "epigenetic therapy". A potential problem in this therapeutic approach is the lack of specificity, as epigenetic modifications are used by both normal and cancer cells to regulate expression of various genes. Ongoing studies to identify genes that are differentially expressed in cancer cells vs. normal cells are providing valuable information about molecular targets for epigenetic therapy. The present article will focus on summarizing some of these studies and will discuss the differences between conventional chemotherapy and epigenetic therapy utilizing epigenetic drugs like DNA methyltransferase inhibitors or histone deacetylase inhibitors. Current perspectives on the future of epigenetic therapy are also discussed.