This review highlights the concept of multiple click reaction strategy which is utilized for design and synthesis of well-defined complex macromolecular structures as well as multifunctionalization of well-defined polymers. This review examines the click combinations mainly from double to quadruple and additionally from the most frequently used to the least. The present review may also be regarded as an update for recent reviews dealing with specifically double and triple click reaction combinations in synthetic polymer chemistry. (c) 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 3147-3165