Tumor cells with neomorphic mutations in IDH1 and IDH2 gain the ability to produce 2-hydroxyglutarate (2-HG), a metabolite involved in the degradation of HIF1α. These mutations are associated with better prognosis in glioma due to downregulation of the HIF1α targets necessary for the switch to aerobic glycolysis. Now, J. Gregory Cairncross and colleagues report that IDH1 and IDH2 mutations in glioma lead to the downregulation of a key metabolic gene, LDHA (encoding lactate dehydrogenase A), through DNA methylation of its promoter (Neuro. Oncol. 16, 686–695, 2014). Using glioma-derived brain tumor stem cells with mutation in IDH1 or IDH2, they found that cell lines that had lost the mutated IDH1 or IDH2 allele continued to hypermethylate the LDHA promoter and underexpress LDHA, even though 2-HG was no longer produced. They further analyzed glioma data from the Repository of Molecular Brain Neoplasia Data and found that LDHA is one of the most downregulated genes in IDH1- and IDH2-mutant gliomas and that patients with low expression of LDHA have a median survival of 50 months, in comparison to 16 months for patients without the mutations. They also analyzed data from The Cancer Genome Atlas and found that IDH1- and IDH2-mutant glioblastomas are associated with high LDHA promoter methylation and low LDHA expression.