Residualizing labels (R-labels) are chemical tags for proteins, originally designed for studies of the sites and mechanisms of plasma protein catabolism. The labels consist of oligosaccharides derivatized with radioactive, fluorescent, nuclear magnetic resonance (NMR), or positron emission tomography (PET) active reporter molecules. Because these glycoconjugates generally have molecular masses in excess of 500 daltons and are hydrophilic, they are relatively membrane impermeant. They are also designed to be resistant to lysosomal hydrolases and are therefore retained inside cells with half-lives of 2-5 days after endocytosis and degradation of the carrier protein. The R-labels thus provide a convenient means for following the cumulative uptake and catabolism of proteins by cells in vivo or in vitro. This review summarizes how R-labels have provided insights into the sites and regulation of the turnover of circulating proteins, and pathways for intracellular transport and degradation of endocytosed proteins. The potential use of R-labels for noninvasive studies of the distribution of protein pharmaceuticals in vivo is also discussed.