The copper catalysis in the Huisgen reaction broadly known as the azide/ alkyne reaction or CuAAC reaction has been discussed. This simple and robust reaction, which involves clusters of Cu and ligands, has led to exclusive formation of the 1,4-isomer. It is vital to maintain a good concentration of Cu throughout the reaction medium particularly in the case of less reactive reaction components or dilute reactions. The ligands' role in protecting the copper from oxidation or disproportionation is also important. The ligands also influence the structure and equilibria of copper clusters and may promote the formation of the most catalytically active copper complexes. The CuAAC reaction may be designed to accommodate all types of protecting groups and reactive intermediates.