Hydrogen bonding, being of similar strength as Van der Waals forces, play a singular role in life as they provide many of the critical, life-sustaining properties of water and also stabilize macromolecular organization producing some of the most consequential outcomes such as stabilization of the structures of proteins and DNA, the building blocks of life. Furthermore, they bestow exceptional tensile and elastic properties to such natural and synthetic polymers as spider silk and cyclic ß-peptide polymers, produced recently in the author’s lab, and afford perplexingly disparate material characteristics to seemingly similar chemical ensembles such as Kevlar and Nomex! Further, the conversion of such bonds, mediated by water, from an intra- to intermolecular variety, within molecular edifices containing them, underpins the chemical and mechanical functioning of the muscle proteins myosin and actin leading to important mechanobiological outcomes. Also, an increasing amount of recent evidence has elucidated their role in the mechanobiology of protein aggregation, i.e. tau and amyloid aggregation, in both mild and acute traumatic brain injury and other neurodegenerative diseases such as Alzheimer’s, cerebral palsy and Alexander’s disease. As obvious from the preceding, indeed, its role in natural and synthetic polymeric systems is versatile, unsurpassed, and exceptionally consequential!