A general, high-yielding and efficient methodology for the copper catalyzed azide-alkyne cycloaddition (CuAAC) reaction catalyzed by in situ generated copper nanoparticles (CuNPs) or their clusters is reported. This simple reaction is facile in water, organic solvents and solvent-free conditions under ambient, open-air conditions and requires no special reaction conditions and chromatographic separation. (C) 2012 Elsevier B.V. All rights reserved.