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 nitrogen side chains of histidine and the relatively neutral pK (ca 6.0) of the histine proton mean that 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.