Drug resistance is a major hurdle in the global battle against tuberculosis (TB). In tackling this problem it is important to understand both how resistance emerges as well as the ways in which multi-drug and extensively drug-resistant TB (M/XDR-TB) may be successfully treated. The biggest problem with treatment is the lack of effective drugs. Exciting developments have been made in this area over recent years with useful drugs being found from older agents as well as new discoveries. Patent applications are being made for novel agents and are also possible as new use for older agents such as thioridazine. A flourishing drug pipeline is critical if we are to make progress in the management of M/XDR-TB.