Semisynthesis is used to create defined analogues of proteins by the chemical manipulation of peptide fragments largely derived from the natural protein and the subsequent reassembly of those fragments into a near-native conformation. In common with the total synthesis of proteins, it requires efficient and non-destructive methods for peptide religation. Recently, a wide range of chemoselective ligation schemes have been elaborated that now permit the assembly of minimally protected peptides from either synthetic or natural sources.