Nutrients such as glucose, fatty acids, amino acids and vitamins are utilized by cellular metabolic pathways to produce metabolites that are used as substrates or activity modulators of chromatin-modifying enzymes. These molecules are included in regulation of the abundance of a plethora of ‘canonical’ modifications, including histone acetylation, histone methylation and DNA methylation, and ‘emerging’ modifications including acylations, homocysteinylation, serotonylation etc. Central-carbon, one-carbon and methionine metabolism, acetate metabolism, ketogenesis and redox-related pathways feed the pools of several of these metabolites, and thus help regulate the epigenomic landscape in concert with chromatin modifiers, remodellers and transcription factors. 2-HG, 2-hydroxyglutarate; αKG, α-ketoglutarate; GlcNAc, β-N-acetylglucosamine; hCys, homocysteine (hcy when a histone modification); MGO, methylglyoxal; PAR, poly(ADP–ribose); SAH, S-adenosylhomocysteine; SAM, S-adenosylmethionine; SucCoA, succinyl-CoA; TCA, tricarboxylic acid.