Mycobacterium tuberculosis (MTB) is a formidable microbial pathogen which uses multiple mechanisms to subvert host immune defences. These include the effective, protective barrier presented by the outer waxy coat, intracellular concealment from host defences, and the ability to enter a prolonged, dormant phase in the infected host. Priority strategies to combat the scourge of TB include the identification of novel and selective targets on/in MTB which are amenable to pharmacological or immune-mediated control. Because they are structurally different from their counterparts in eukaryotic cells and are likely to be essential for survival and growth, the major K+ transporters of MTB represent alternative and novel targets for drug and vaccine design. These K+-uptake systems of MTB are the primary focus of this review, with particular emphasis on their genomic and protein structures, properties and functions, and potential roles in intracellular survival.