Fuente: Ultrasounds Extraction Byproducts Click chemistry is a synthetic strategy that enables the formation of heteroatom-based systems. It provides both stereoselectivity and regioselectivity, along with high yields, under mild reaction conditions. These features make this chemical strategy inherently characterized by complete atom economy and reduced waste production. Nevertheless, since its inception, several upgrades have been implemented to further enhance the overall sustainability of this process, such as replacing fossil fuel-derived and hazardous solvents, introducing recoverable heterogeneous catalysts, and establishing continuous flow synthesis and/or using alternative energy sources. In this chapter, we aim to focus on the most significant green achievements that have contributed significantly to greening this useful transformation and reducing its environmental and human health footprint.