The nucleophilic conjugate substitution of α-(substituted methyl)acrylate is a very convenient reaction that occurs at ambient temperature with a variety of nucleophiles, such as amines, thiols, phenols, enols and carboxylic acids. The reaction is quantitative when the nucleophile and leaving group have distinctly different acidities, whereas it becomes dynamic and reversible if their acidities are similar. This review describes the fundamentals and applications of conjugate substitution reactions in polymer chemistry, particularly in monomer synthesis, end-group incorporation, end-functionalization, polycondensation, and main chain scission.