A review of efforts that have provided total syntheses of vancomycin and related glycopeptide antibiotics, their agylcons, and key analogues is provided. It is a tribute to: developments in organic chemistry and the field of organic synthesis that not only can molecules of this complexity be prepared today by total synthesis but such efforts can be extended to the preparation of previously inaccessible key analogues that contain deep-seated structural changes. With the increasing prevalence of acquired bacterial resistance to existing classes of antibiotics and with the emergence of vancomycin-resistant pathogens (VRSA and VRE), the studies pave the way for the examination of synthetic analogues rationally designed to not only overcome vancomycin resistance but provide the foundation for the development of even more powerful and durable antibiotics.