The purpose of this critical review is to introduce the reader to an increasingly important class of phenomena: enormous changes in rates of simple chemical reactions within macromolecules as they are stretched by interactions with the environment. In these chemomechanical, or mechanochemical, phenomena the effect of the macromolecular environment can be visualized as a spring (harmonic or anharmonic) bridging and pulling apart a pair of atoms of the macromolecule. Being able to predict how the parameters of this spring affect the kinetics of the reactions occurring between the constrained atoms may create revolutionary opportunities for designing new reactions, molecules and materials that would capture large-scale deformations to drive useful chemistry or, conversely, that would propel autonomous micro- and nanomechanical devices by coupling them to the concerted motion of atoms that convert reactants into products. Although chemists have long studied and exploited coupling between molecular strain and reactivity in small molecules, a quantitative understanding of the relationship between large-scale (>50 nm) strain and localized reactivity presents unique conceptual and experimental challenges. Below we discuss both the phenomenology and the interpretive framework of chemomechanical phenomena (102 references).