In order to construct biologically active materials for applications in nanotechnology and medicine, materials scientists have extensively explored the use of nature-derived building blocks, in particular amino acids, carbohydrates, and lipids. Typically, these building blocks are assembled into larger arrays, or attached to synthetic scaffolds or other biomolecules, in such a way that novel biohybrid materials can be obtained with new or improved properties. To ensure that the original activity of the building blocks herein is preserved, the construction of biohybrid materials needs to proceed in a well-defined manner employing selective coupling techniques with a high functional group tolerance. Consequently, the concept of "click chemistry" has rapidly established a prominent role in the synthesis of these types of biologically active materials. In particular, the Cu-catalyzed Azide-Alkyne [3 þ 2] Cycloaddition (CuAAC) has proven to be extremely valuable to many researchers in the field of biohybrid materials science, including our own groups. This mini-review will focus on the application of the CuAAC in the construction of biohybrid materials and will discuss our recent efforts as well as related work from other groups.