Cancer was thought to be caused solely by genetic mutations in oncogenes and tumor suppressor genes. In the last 35 years, however, epigenetic changes have been increasingly recognized as another primary driver of carcinogenesis and cancer progression. Epigenetic deregulation in cancer often includes mutations and/or aberrant expression of chromatin-modifying enzymes, their associated proteins, and even non-coding RNAs, which can alter chromatin structure and dynamics. This leads to changes in gene expression that ultimately contribute to the emergence and evolution of cancer cells. Studies of the deregulation of chromatin modifiers in cancer cells have reshaped the way we approach cancer and guided the development of novel anticancer therapeutics that target epigenetic factors. There remain, however, a number of unanswered questions in this field that are the focus of present research. Areas of particular interest include the actions of emerging classes of epigenetic regulators of carcinogenesis and the tumor microenvironment, as well as epigenetic tumor heterogeneity. In this review, we discuss past findings on epigenetic mechanisms of cancer, current trends in the field of cancer epigenetics, and the directions of future research that may lead to the identification of new prognostic markers for cancer and the development of more effective anticancer therapeutics.