According to the types of stem cells and considering tumor evolution, one of the most significant theories about stem cells is derived from cancer stem cells (CSCs), which, similar to normal adult stem cells, possess the capacity of self-renewal and potential of differentiation. Over the past few years, compelling evidence has emerged in support of the CSC model for many tumors. The CSCs are posited to be responsible not only for tumor initiation but also for tumor metastasis, relapse and therapyresistance. Thus, understanding the mechanisms that govern the generation and maintenance of this special population of cells is of great importance. Despite the current progress in basic genetic research, the latest work implies that epigenetic mechanisms, from DNA methylation, histone modifications and chromatin-remodeling to the wide discovered miRNAs, play critical roles in the regulation of CSC features. This review focuses on the key epigenetic mechanisms that regulate and define the unique CSC properties.