It has been very satisfying to put together this Special Edition of The Review of Diabetic Studies on C-peptide and diabetes. We are greatly encouraged by the advances being made in this research area, and especially to see the beneficial effects of C-peptide making their way into clinic. Once regarded as a redundant waste product of insulin synthesis, C-peptide is now recognized as an important regulatory hormone in its own right. Our understanding of C-peptide physiology is expanding rapidly. It is abundantly clear that C-peptide deficiency in type 1 diabetes plays important pathogenetic roles in the development of various complications, with consequent beneficial effects upon C-peptide replacement.