Proteins contain mainly weak, conventional hydrogen bonds; however, a few enzymes have low barrier hydrogen bonds (LBHBs) in transition state analog complexes. Hydrogen bonds display variations in physicochemical properties including length, spectroscopic characteristics, and strength. Three classes of hydrogen bonds have been defined – weak (2–8 kcal mol −1 ), strong (10−2 kcal mol −1 ), and very strong (24−40 kcal mol −1 ). In a weak hydrogen bond, the proton is bonded to one heteroatom by a dipolar covalent bond and engages in a weak electrostatic attraction with another heteroatom. In a strong hydrogen bond, or LBHB, the heteroatoms are closer than a van der Waals contact, the covalent bond to the proton is elongated, and the contact between the proton and the second heteroatom is significantly shorter than in a weak hydrogen bond. In a very strong, or single-well hydrogen bond, the heteroatoms are much closer than a van der Waals contact, and the proton is nearly centered between them. LBHBs in proteins and small molecules are characterized by their spectroscopic and thermodynamic properties, deuterium fractionation factors, and crystallographic structures. LBHBs have been identified in transition state analog complexes of a few enzymes and are postulated to stabilize the transition states in catalysis.