There is an urgent need for new antimycobacterial drugs, and in particular for novel agents that will shorten the duration of tuberculosis chemotherapy, or overcome drug-resistant strains of the causative organism, Mycobacterium tuberculosis. Our knowledge of the tubercle bacillus and its complex interaction with the human host has improved dramatically in recent years, particularly with the determination of its complete genome sequence. New genome-scale tools are being applied to aid in drug target identification, alongside traditional approaches aimed at understanding the basic biology of M. tuberculosis. Many potential drug targets have been identified, but very few have been validated by showing that they are essential for growth or survival of the bacterium. In this review, the landscape of potential drug targets is surveyed.