The origin of the extraordinary catalytic activity of gold nanoparticles is discussed on the basis of density-functional calculations, adsorption studies on single crystal surfaces, and activity measurements on well characterized supported gold particles. A number of factors are identified contributing to the activity, and it is suggested that it is useful to consider lowcoordinated Au atoms as the active sites, for example, CO oxidation and that the effect of the support can be viewed as structural and electronic promotion. We identify the adsorption energy of oxygen and the Au-support interface energy as important parameters determining the catalytic activity.