Since 1953, leptospirosis has been recognized as a public health problem in Réunion. In 2004, a dedicated surveillance system was established, involving the systematic reporting of cases and the conduct of environmental investigations around hospitalized patients. Here we present a summary of data from 12 years of surveillance. From 2004 to 2015, 611 cases were reported (6 cases per 100,000 inhabitants). Of these, 568 (93%) were hospitalized, including 33% in intensive care units. The average annual case-fatality rate was 3%. Men accounted for 93% of hospitalized cases and 85% of non-hospitalized cases (a non-significant difference). The incidence varied by year (from 3 to 10 cases per 100,000 inhabitants) and by municipality on the island (from 2 to 63 cases per 100,000 inhabitants). Professional or recreational agricultural activities accounted for 65% of exposure routes. Occupational exposures accounted for 20% of cases, primarily in occupations at high risk for leptospirosis. Recreational exposures have not surpassed agricultural or occupational exposures, as is the case in temperate countries. According to the new surveillance system implemented in 2004, the number of reported cases has steadily increased since that year. This situation is partly due to the implementation of this new system, but also to a real increase in the number of detected cases resulting from the introduction of molecular diagnostic methods and the increased biological investigation of dengue-like syndromes by the island’s practitioners since the 2006 chikungunya crisis. The possibility of an epidemic was also always present, due to climatic events such as Cyclone Bejiza in 2014. Given the severity of its forms, leptospirosis remains a public health problem in Réunion. Raising awareness among healthcare professionals about the disease and its aggravating factors, as well as tailoring prevention measures to the most at-risk populations—including vaccination against Leptospira icterohaemorrhagiae for high-risk professionals—are key priorities for reducing the incidence and fatality rate of leptospirosis in Réunion.