Undecagold cluster labeling of reactive cysteine residues in numerous proteins has allowed the labeled sites to be identified by electron microscopy providing high-resolution information on the location and orientation of subunits in oligomeric enzymes, virus capsids, crystalline sheets of membrane proteins, and muscle thin filaments, The range of applications of undecagold cluster labeling has been greatly extended by the availability of site-directed mutagenesis to introduce cysteine residues at sites of interest. In this paper I discuss factors that can influence the extent and specificity of labeling, methods for biochemical analysis of uni decagold-labeled proteins, and the effects of undecagold cluster labeling on biological activity.