Over the past decade, bioorthogonal click chemistry has led the field of biomaterial science into a new era of diversity and complexity by its extremely selective, versatile, and biocompatible nature. In this viewpoint, we seek to emphasize recent endeavors of exploiting this versatile chemistry toward the development of poly(ethylene glycol) hydrogels as cell culture scaffolds. In these cell-laden materials, the orthogonality of these reactions has played an effective role in allowing the creation of diverse biochemical patterns in complex biological environments that provide new found opportunities for researchers to delineate and control cellular phenotypes more precisely than ever.