MicroRNAs (miRNAs) are approximately 22 nt non-coding RNAs, which regulate gene expression in a sequence-specific manner via translational inhibition or messenger RNA (mRNA) degradation. Since the discovery of their fundamental mechanisms of action, the field of miRNAs has opened a new era in the understanding of small noncoding RNAs. By molecular cloning and bioinformatic approaches, miRNAs have been identified in viruses, plants and animals. miRNAs are predicted to negatively target up to one-third of human mRNAs. Cancer is a complex genetic disease caused by abnormalities in gene structure and expression. Previous studies have heavily focused on protein-coding genes; however, accumulating evidence is revealing an important role of miRNAs in cancer. Epigenetics is defined as mitotically and/or meiotically heritable changes in gene expression that are not accompanied by changes in DNA sequence. Given the critical roles of miRNAs and epigenetics in cancer, characterizing the epigenetic regulation of miRNAs will provide novel opportunities for the development of cancer biomarkers and/or the identification of new therapeutic targets in the foreseeable future.