This review uses the total synthesis of vancomycin analogues by Boger and his colleagues as a case study of the drug discovery process. Vancomycin is a glycopeptide antibiotic used to treat staphylococcal infections. It acts by binding to the terminal chains attached to peptidoglycan in bacterial cell walls, which blocks these chains from crosslinking with each other. This inability to crosslink prevents the bacterium from forming a cell wall, ultimately resulting in bacterial cell death. However, over time, bacteria have evolved resistance to vancomycin. In response to this, Boger and his team studied single atom changes (O, S, NH) in the chemical structure of vancomycin to create new vancomycin analogues that these bacteria are not resistant to. The drug discovery process involves upstream and downstream flow of information about a potential drug candidate, and the interlude of Boger's work with vancomycin elegantly demonstrates this process. Boger found that replacing a single oxygen atom in vancomycin with NH significantly increases the ability of the analogue to bind with peptidoglycan terminal chains, increasing its effectiveness as an antibiotic.