Graphene oxide (GO) is a 2D nanomaterial with unique chemistry due to the combination of sp2 hybridization and oxygen functional groups (OFGs) even in single layer. OFGs play a fundamental role in the chemical functionalization of GO to produce GO-based materials for diverse applications. However, traditional strategies that employ epoxides, alcohols, and carboxylic acids suffer from low control and undesirable side reactions, including by-product formation and GO reduction. Thiol-ene “click” reaction offers a promising and versatile chemical approach for the alkene functionalization (−C=C−) of GO, providing orthogonality, stereoselectivity, regioselectivity, and high yields while reducing by-products. This review examines the chemical functionalization of GO via thiol-ene “click” reactions, providing insights into the underlying reaction mechanisms, including the role of radical or base catalysts in triggering the reaction. We discuss the “how” and “where” the reaction takes place on GO, the strategies to avoid unwanted side reactions, such as GO reduction and by-product formation. We anticipate that multi-functionalization of GO via the alkene groups will enhance GO physicochemical properties while preserving its intrinsic chemistry.