Traditional glycero-phospholipids have been extensively studied with varying head groups and hydrocarbon chains. Glycero-phospholipid backbone modifications represent a smaller family of modified phospholipids, and as discussed in this review, these derivatives were prepared for a variety of different needs and physical studies. The ability to chemically-tailor the structure of these amphiphiles combined with the propensity of these amphiphiles to form supramolecular structures of varying size and complexity provides innumerable opportunities for fundamental studies as well as for applications in medicine and biotechnology.