In spite of effective antibiotics to treat TB (tuberculosis) since the early 1960s, we enter the new millennium with TB currently the leading cause of death from a single infectious agent, killing more than 3 million people worldwide each year. Thus an understanding of drug-resistance mechanisms, the immunobiology of cell wall components to elucidate host-pathogen interactions and the discovery of new drug targets are now required for the treatment of TB. Above the plasma membrane is a classical chemotype IV peptidoglycan to which is attached the macromolecular structure, mycolyl-arabinogalactan via a unique diglycosylphosphoryl bridge. The present review discusses the assembly of the mAGP (mycolyl-arabinogalactan-peptidoglycan) complex and the site of action of EMB (ethambutol), bringing forward a new era in TB research and focus for new drugs to combat multidrug-resistant TB.