Leptospirosis is a cosmopolitan zoonosis caused by bacteria of the genus Leptospira. The hot and humid climate of the intertropical zone is particularly conducive to its spread. In French Guiana, a French department located in the Amazon region of northeastern South America, the disease appears to be rare. The objective of this article is to summarize the current state of knowledge regarding the epidemiology of human leptospirosis in French Guiana and to discuss prospects for improving surveillance. Publications on leptospirosis in French Guiana are scarce and dated, ranging from the 1940s to 1995. Annual reports from the National Reference Center for Leptospirosis (CNR, Institut Pasteur de Paris) show a fairly stable annual number of cases between 1996 and 2012, ranging from 6 to 18 depending on the year, with a significant increase from 2013 to 2015: 36, 92, and 67 cases per year, respectively. A recent retrospective study of cases occurring between 2007 and 2014, identified using very strict diagnostic criteria, recorded 72 cases in the department, including 12 (16.7%) severe cases and 3 (4.2%) deaths. The disease primarily affected men (86.1%) aged 20 to 49 (63.9%). It is likely that leptospirosis is an underdiagnosed disease in the region, due to the lack of readily available diagnostic tools, clinicians’ limited familiarity with this condition, and the presence of numerous other diseases with similar clinical symptoms in the acute phase (malaria, arboviruses, Q fever, Amazonian toxoplasmosis). Larger-scale studies are needed to determine the true impact of this disease in French Guiana.