Mechanical activation of chemical bonds is usually achieved by applying external forces. However, nearly all molecules exhibit inherent strain of their chemical bonds and angles as a result of constraints imposed by covalent bonding and interactions with the surrounding environment. Particularly strong deformation of bonds and angles is observed in hyperbranched macromolecules caused by steric repulsion of densely grafted polymer branches. In addition to the tension amplification, macromolecular architecture allows for accurate control of strain distribution, which enables focusing of the internal mechanical tension to specific chemical bonds and angles. As such, chemically identical bonds in self-strained macromolecules become physically distinct because the difference in bond tension leads to the corresponding difference in the electronic structure and chemical reactivity of individual bonds within the same macromolecule. In this review, we outline different approaches to the design of strained macromolecules along with physical principles of tension management, including generation, amplification, and focusing of mechanical tension at specific chemical bonds.