<p><b>PURPOSE OF REVIEW: </b>It has only recently become apparent that mutations in epigenetic mechanisms and perturbation of epigenomic patterning are frequent events in B-cell lymphomas. The purpose of this review is to highlight these new findings and provide a conceptual framework for understanding how epigenetic modifications might contribute to lymphomagenesis.</p><p><b>RECENT FINDINGS: </b>Somatic mutations affecting histone methyltransferases such as enhancer of zeste 2 and mixed lineage leukemia 2, histone demethylases including ubiquitously transcribed X chromosome tetratricopeptide repeat and Jumonji domain-containing 2C, and histone acetyltransferases including CBP and p300 are recurrent and common in lymphomas. These mutations result in disruption of chromatin structure and functions of other proteins, ultimately causing aberrant transcriptional programming affecting multiple gene networks. Widespread perturbation of cytosine methylation patterning now appears to be a hallmark of B-cell lymphomas and occurs in specific patterns that can distinguish disease subtypes. Therapeutic targeting strategies can overcome abnormal epigenetic mechanisms and potently kill lymphoma cells.</p><p><b>SUMMARY: </b>Newly discovered epigenetic lesions may provide critical insights into the genesis of B-cell lymphomas, but further studies are required to understand how they affect biological mechanism. Epigenetic lesions offer tremendous opportunities for the development of improved biomarkers and treatments.</p>