Surface-induced dissociation (SID) was first introduced as an ion activation method for tandem mass spectrometry in the laboratory of Graham Cooks at Purdue University. Early studies focused on small molecules that could be ionized and fragmented by the instruments available at that time. It was predicted that SID would someday be applied to much more massive ions and that the large collision target (the surface) would be advantageous for dissociation of very large ions. This chapter describes the development of SID from its early days until the present, closing with examples that illustrate the benefits of using SID to cleave large noncovalent protein complexes.