Common pathways and mechanisms can be found in both cancers and inborn errors of metabolism. 2‐Hydroxyglutarate (2‐HG) acidurias and isocitrate dehydrogenase (IDH) 1/2 mutant tumors are examples of this phenomenon. 2‐HG can exist in two chiral forms, D(R)‐2‐HG and L(S)‐2‐HG, which are elevated in D‐ and L‐acidurias, respectively. D‐2‐HG was subsequently discovered to be synthesized in IDH 1/2 mutant tumors including ∼70% of intermediate‐grade gliomas and secondary glioblastomas (GBM). Recent studies have revealed that L‐2‐HG is generated in hypoxia in IDH wild‐type tumors. Both 2‐HG enantiomers have similar structures as α‐ketoglutarate (α‐KG) and can competitively inhibit α‐KG‐dependent enzymes. This inhibition modulates numerous cellular processes, including histone and DNA methylation, and can ultimately impact oncogenesis. D‐2‐HG can be detected in vivo in glioma patients and animal models using advanced imaging modalities. Finally, pharmacologic inhibitors of mutant IDH 1/2 attenuate the production of D‐2‐HG and show great promise as therapeutic agents.