MicroRNAs (miRNAs) are master regulators of gene expression at the posttranscriptional level. The unique tissue-specific expression of miRNA, when altered, leads to aberrant gene regulations, oncogenic signaling, and deregulated cellular pathways, transforming a normal cell into a cancer cell. The control of miRNA expression is strongly influenced by the epigenetic modifications occurring at an early stage of cellular transformation. The epigenetic changes potentially determine the chromatin accessibility and transcriptional assembly by simple base modifications. The well-known phenomenon of DNA methylation, histone methylation, and acetylation is therefore the dictator of the mighty miRNAs. The promoter regions of tumor suppressor miRNA genes are found to be hypermethylated, diminishing their transcriptional efficiency. The promoters of oncogenic microRNAs are often demethylated, releasing the tight control on miRNA transcription. The chromatin state is relaxed due to histone deacetylation or demethylation, facilitating the accessibility for an active transcription complex at the miRNA genes. Surprisingly, miRNAs are observed to be regulating the enzymes like DNMTs and HDACs that catalyze such epigenetic modifications. Therefore, DNMT, HDAC, and HAT inhibitors are being proficiently used in combinatorial cancer therapy. This chapter gives an exclusive insight into the regulatory inter-relationship of the epigenetic factors and miRNAs in cancer, with a highlight on the role of RNA methylation in miRNA biogenesis.