Although much remains to be learned, our understanding of the mechanisms and processes by which insulin is degraded has advanced considerably over the past few years. The roles of receptor binding and internalization in mediating insulin degradation have been clarified, and the endosomal pathway for intracellular insulin degradation has been established and partially characterized. The importance of IP (IDE) in cellular insulin degradation has been established and the importance of lysosomal degradation questioned. Studies on IP have identified the degradation products resulting from insulin metabolism by this enzyme and shown that the degradation products by IP are identical with those produced by isolated hepatocytes. A major remaining question for future investigation is the potential role of insulin degradation and intracellular processing in insulin action.