Surveys of the global burden of disease have established that formidable health problems loom as the new millennium approaches. In both industrialized and developing countries lung disease is particularly problematic. Tuberculosis provides a concrete example of the ability of existing interventions such as directly observed therapy (DOT) to save millions of lives in the immediate future and the potential for new knowledge and tools to eventually eliminate the disease. Molecular epidemiology shows the potential of new technology to supplement established approaches in answering questions central to public health. Our knowledge of the complete genomic sequence of Mycobacterium tuberculosis now has us poised on the brink of a new era. Emerging technologies such as microscopic arrays comprised of thousands of spots of DNA will provide knowledge that will fundamentally alter our approach to disease control. The synergy of a balanced portfolio incorporating a globalized public health commitment and creative basic research will provide us with the infrastructure and tools needed to eliminate tuberculosis before the close of the 21st century.