Summary Health services in Africa are being overburdened by a continuous increase of cases of tuberculosis (TB), largely resulting from the large pool of infected individuals becoming co-infected with HIV. To help deal with the situation, TB treatment schedules need to be shorter and simpler, with minimal contact between the patient and the service provider required, if the problems of non-compliance and of ineffective service provision are to be overcome. Various drugs not marketed for use in the treatment of TB are currently under investigation for their potential roles in the simplification or shortening of treatment schedules. These mainly include the long-acting rifamycins and the fluoroquinolones. Furthermore, new drug development is focused on an understanding of the host–pathogen interaction leading to infection, latency and disease. Of these, latency is least understood. The use of molecular diversity and combinatorial chemistry, proteomics, and the use of the whole genome to discover drug targets are expected to produce new lead compounds for turning into drugs to treat active, latent and multi-drug-resistant TB more effectively in the foreseeable future.