Leptospirosis is the most wide spread zoonosis worldwide; it is present in all continents except Antarctica and evidence for the carriage of Leptospira has been found in virtually all mammalian species examined. Humans most commonly become infected through occupational, recreational, or domestic contact with the urine of carrier animals, either directly or via contaminated water or soil. Leptospires are thin, helical bacteria classified into at least 12 pathogenic and 4 saprophytic species, with more than 250 pathogenic serovars. Immunity following infection is generally, but not exclusively, mediated by antibody against leptospiral LPS and restricted to antigenically related serovars. Vaccines currently available consist of killed whole cell bacterins which are used widely in animals, but less so in humans. Current work with recombinant protein antigens shows promise for the development of vaccines based on defined protective antigens. The cellular and molecular basis for virulence remains poorly understood, but comparative genomics of pathogenic and saprophytic species suggests that Leptospira expresses unique virulence determinants. However, the recent development of defined mutagenesis systems for Leptospira heralds the potential for gaining a much improved understanding of pathogenesis in leptospirosis. Copyright 2009 Elsevier B.V. All rights reserved.