Leptospirosis is among the most important zoonotic disease worldwide. Annually, millions of human cases occur worldwide, with case fatality rates ranging as high as 20-25% in some regions. The pathogenicity of the Leptospira spp is depending on the responsible serovar. Rodents are the most important primary hosts but a wide range of other mammals are also able to carry and transmit the disease as secondary hosts. Humans become infected directly through infected animal contact or indirectly with water, food, or soil containing urine from these infected animals. The main route of infection is the skin through skin abrasions, more rarely through mucosa contact and exceptionally by respiratory or digestive route. The diagnosis should be evoked on a detailed personal history evoking epidemiological context with consistent clinical and biological results. A lot of infected persons may have no symptoms at all showing a minor illness. In most cases symptoms are flu-like with fever, headache and intensive myalgia associated with hepatic cytolysis, proteinuria and thrombocytopenia. In France, the most common clinical presentation combines liver involvement and jaundice with kidney involvement. However, other sites can be involved (brain, heart and lung). The diagnosis is often obtained several weeks later by serology. Treatment for leptospirosis is based on an early antibiotic therapy with amoxicillin, or tetracycline in case of allergy, but it remains controversial whether antimicrobials produce a beneficial effect in mild human leptospirosis. For at-risk occupations, preventive treatment recommends eviction or limitation of exposure, and vaccination.