Mycobacteria contribute substantially to human infectious disease, most notably the primary pathogens of tuberculosis (TB), leprosy and Bureli ulcer. Global prospects for TB control are challenged by the emergence of drug-resistant strains. If we are to stay ahead of mycobacterial strains developing resistance to chemotherapeutic regimens, all new agent leads must be explored. Lantibiotics, either native or bio-engineered, represent one such avenue to enhance our artillery against drug-resistant strains.