Macromolecular substitution is a process in which the side groups of a polymer are replaced after a precursor polymer has been synthesized. This contrasts with conventional polymer syntheses in which the side groups are present in the monomer from which the polymer is derived. Macromolecular substitution allows the synthesis of polymers with side groups that would not survive or would inhibit a classical polymerization process. The most extensive use of macromolecular substitution is found in polyphosphazenes where a reactive polymeric precursor, poly(dichlorophosphazene), (NPCl2)n, serves as a platform for chlorine replacement by a wide range of organic, inorganic, or organometallic nucleophiles to yield several hundred polymers with unique properties and uses. A related platform uses poly(difluorophosphazene), especially for organometallic side groups. Hybrid polymers with both phosphazene and classical organic or organosilicon components are also accessible. A wide range of uses has been developed for poly(organophosphazenes) including biomedical devices, fire-resistant coatings, foams and seals, films and fibers, low-temperature elastomers, radiation-resistant materials, and optical devices.