Cellular proteins are marked for selective degradation by their ligation to the polypeptide ubiquitin. Recent studies have revealed information on the mechanisms involved in the selection of proteins for ligation to ubiquitin and on the mode of degradation of ubiquitinated proteins. Much remains to be learned about the high selectivity of this degradation pathway. Recent evidence that the cell-cycle regulatory proteins, cyclins, are degraded by the ubiquitin pathway points the way to future challenges in ubiquitin research.