Molecular biomechanics includes two themes: the study of mechanical aspects of biomolecules and the study of molecular biology of the cell using mechanical tools. The two themes are interconnected for obvious reasons. The present review focuses on one of the interconnected areas-the mechanical regulation of molecular interaction and conformational change. Recent conceptual developments are summarized, including catch bonds, regulation of molecular interaction by the history of force application, and cyclic mechanical reinforcement. These studies elucidate the mechanochemistry of some of the candidate mechanosensing molecules, thereby providing a natural connection to mechanobiology.