This review is a personal memoir of the history of proteolipids and is limited to aspects of the field with which the author has been involved in one way or another. The discovery of proteolipids was a serendipitous observation made in the course of the study of sulfatides. Initial focus was on the chemical characterization of brain proteolipids, their behavior under different conditions and their identification as the major protein of CNS myelin. The sequence of PLP was obtained using solid phase protein sequencing techniques. This, in turn, made possible a new era in which biochemical, cellular and molecular approaches could be applied to address new questions about PLP. Identification of genetic defects in the PLP molecule and its regulation has contributed to understanding myelin biology. Studies of the encephalitogenic activity of PLP in animal models have influenced the views of inflammatory processes in multiple sclerosis. Despite remarkable progress, much remains to be learned about the structure and function of PLP.