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Leptospirosis, a spirochaetal zoonotic disease, has been recognized as an important emerging infectious disease in the last 10 years. This review addresses the issues in the epidemiology, diagnosis and clinical management which confront public health responses, and highlights the progress made towards understanding the Leptospira genome, biology and pathogenesis.Leptospirosis has spread from its traditional rural base to become the cause of epidemics in poor urban slum communities in developing countries. Mortality from severe disease forms, Weil's disease and severe pulmonary haemorrhage syndrome, is high (>10% and >50%, respectively) even when optimal treatment is provided. Moreover, the overall disease burden is underestimated, since leptospirosis is a significant cause of undifferentiated fever and frequently not recognized. Barriers to addressing this problem have been the lack of an adequate diagnostic test and effective control measures. China and Brazil, countries in which leptospirosis is a major health problem, have completed the sequence of the Leptospira interrogans genome. Together with new genetic tools and proteomics, new insights have been made into the biology of Leptospira and the mechanisms used to adapt to host and external environments. Surface-exposed proteins and putative virulence determinants have been identified which may serve as sub-unit vaccine candidates.Major progress has been made in the basic research of leptospirosis. Future challenges will be to translate these advances into public health measures for developing countries. Yet the most effective responses may be interventions that directly address the determinants of poverty, such as poor sanitation, which are often responsible for transmission.