In this section, we discuss evidence that mutations in or overexpression of histone methyltransferases or demethylases mediates metabolic reprogramming in cancer cells, focusing on enhancer of zeste homolog 2 (EZH2), euchromatic histone lysine methyltransferase 2 (EHMT2), lysine methyltransferase 2D (KMT2D), and lysine-specific histone demethylase 1 (LSD1). Here, KMT2D is linked to cancer.