The article by Jason E. Hein and Valery V. Fokin reviews the Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) reaction, a widely used and reliable method for forming covalent bonds between functional groups. The reaction, which has been applied in various fields such as organic synthesis, medicinal chemistry, and bioconjugation, involves the coordination of copper(i) acetylide complexes. The review highlights the history, key mechanistic aspects, and practical applications of CuAAC, emphasizing the importance of understanding and controlling the reversible steps involving copper(i) acetylide equilibria. The authors discuss the advantages of CuAAC over other methods, such as its robustness, ease of use, and broad compatibility with functional groups and solvents. They also explore the role of different catalysts and ligands, including the use of ascorbate to maintain the catalytic cycle under oxygen-free conditions. The review further delves into the mechanism of CuAAC, explaining the formation of copper(i) acetylide intermediates and the role of dinuclear complexes. Additionally, the article covers the reactivity of 1-iodoalkynes and sulfonyl azides under CuAAC conditions, and the synthesis of 1-sulfonyl triazoles as precursors to azavinyl carbenes. The authors conclude by emphasizing the importance of CuAAC in chemical science and the challenges and opportunities in designing new ligands and conditions for this complex catalytic process.The article by Jason E. Hein and Valery V. Fokin reviews the Copper-catalyzed Azide-Alkyne Cycloaddition (CuAAC) reaction, a widely used and reliable method for forming covalent bonds between functional groups. The reaction, which has been applied in various fields such as organic synthesis, medicinal chemistry, and bioconjugation, involves the coordination of copper(i) acetylide complexes. The review highlights the history, key mechanistic aspects, and practical applications of CuAAC, emphasizing the importance of understanding and controlling the reversible steps involving copper(i) acetylide equilibria. The authors discuss the advantages of CuAAC over other methods, such as its robustness, ease of use, and broad compatibility with functional groups and solvents. They also explore the role of different catalysts and ligands, including the use of ascorbate to maintain the catalytic cycle under oxygen-free conditions. The review further delves into the mechanism of CuAAC, explaining the formation of copper(i) acetylide intermediates and the role of dinuclear complexes. Additionally, the article covers the reactivity of 1-iodoalkynes and sulfonyl azides under CuAAC conditions, and the synthesis of 1-sulfonyl triazoles as precursors to azavinyl carbenes. The authors conclude by emphasizing the importance of CuAAC in chemical science and the challenges and opportunities in designing new ligands and conditions for this complex catalytic process.