Leptospirosis, caused by spirochetes of the genus Leptospira, has increasingly been recognized to affect travelers and residents in tropical settings. A zoonotic disease, leptospirosis is transmitted to humans through environmental surface waters contaminated by the urine of chronically infected mammals. Outcome of infection varies, ranging from acute febrile illness (including self-resolving undifferentiated fever) to aseptic meningitis to a fulminant syndrome of jaundice, oliguric renal failure, pulmonary hemorrhage, and refractory shock. Hospitalized cases have mortality rates as high as 25%. A recent clinical trial showed that third-generation cephalosporin is as effective as doxycycline and penicillin in the treatment of acute disease. Doxycycline is effective in preventing leptospirosis in travelers. No protective vaccine is currently available.