Oncogenic mutations in isocitrate dehydrogenase (IDH) are seen in cholangiocarcinoma, low grade gliomas, glioblastomas, chondrosarcoma, and acute myeloid leukemias and myelodysplastic syndromes. Targeted therapies using inhibitors of mutant IDH are now used to treat leukemias with IDH mutations. Mutant IDH produces 2-hydroxyglutarate, an oncometabolite that alters the activity of epigenome regulatory enzymes, leading to epigenetic changes like DNA methylation and histone modification that change cancer gene expression and drive cellular transformation and oncogenesis.