Histidine is one of the 20 most common natural amino acids, coded for in DNA. Nutritionally, in humans, histidine is considered an essential amino acid, but only in children. The imidazole side chains of histidine and the relatively neutral pK (ca 6.0) mean that relatively small shifts in cellular pH will change its charge. For this reason, this amino acid side chain finds its way into considerable use as a coordinating ligand in metalloproteins, and also as a catalytic site in certain enzymes.

The amino acid is a precursor for histamine biosynthesis.