Dysregulation of gene expression is a frequent occurrence in oral squamous cell carcinoma (OSCC). However, accumulating evidence suggests that in contrast to genetics, epigenetic modifications consisting of aberrant DNA methylation, histone modifications and altered expression of miRNAs induce OSCC tumorigenesis and perhaps play a more central role in the evolution and progression of this disease. The unifying theme among these three epigenetic mechanisms remains the same, which is aberrant regulation of gene expression. In this article, we provide a comprehensive review of the impact of epigenetics on oral tumorigenesis with a systematic report on aberrant DNA methylation, histone modifications and miRNA regulation in the pathogenesis of OSCC. We provide insights into recent studies on the prospect of biomarkers for early detection and indication of disease recurrence, and novel treatment modalities.