Through rigorous spectroscopic characterizations, including in situ, real-time monitoring, and size-exclusion chromatography (SEC) we describe the functionalization of polymers and copolymers based on vinyl dimethyl azlactone (VDMA), as well as modification of the VDMA monomer using efficient ring-opening strategies. Specifically, we demonstrate modification of VDMA-based materials by "pegylation", base-catalyzed ring-opening hydrolysis, and nucleophilic addition of short alkyl chains, fluorescent markers, and motifs used to specifically bind proteins. All of these functionalizations take advantage of the susceptibility of the pendant azlactone ring of VDMA to undergo nucleophilic attack. Polymers as well Lis copolymers incorporating vinyl pyrrolidone were synthesized by conventional free radical polymerization and thoroughly characterized by FTIR, H-1 NMR, C-13 NMR, SEC, thermogravimetric analysis and differential scanning calorimetry prior to modification. The variety of conjugations and ease of transformations enabled by use of the reactive yet hydrolytically stable VDMA-based materials inspires a broad range of applications for these soft materials.