In spite of effective antibiotics to treat tuberculosis in the late 1950s and early 1960s we enter the new millennium with tuberculosis (TB) currently the leading cause of death from a single infectious agent, killing more than three 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 (often referred to as the mAGP complex). Clearly, cell wall assembly is a profitable choice for the design of novel anti-TB agents. In addition, new targets within the complex may be identified as well as establishing the mode of action of existing agents, mechanisms of drug resistance and the immunomodulatory role of cell wall constituents. In summary, the presentation will discuss the assembly of the mAGP, it’s associated lipids and the site of action of several major anti-TB drugs, along with the completion of the TB genome bringing forward a new era in TB research and focus for new drugs to combat multi-drug resistant TB.