Leptospirosis is the most important zoonosis in the world, and the causative agents are microorganisms belonging to the genus Leptospira. Mild symptoms are observed in 90% of cases, and include fever, headache, anorexia, conjunctival suffusion, diarrhea, nausea, vomiting, malaise, and myalgia. Severe form, called Weil syndrome, is characterized by acute kidney injury (AKI), jaundice, and pulmonary hemorrhage. Several mechanisms contribute to AKI in leptospirosis. There is direct nephrotoxic action of the microorganism and toxin effects, leading to immune response induction in the pathogenesis of AKI. Indirect effects also contribute to AKI, such as dehydration, hemodynamic instability, rhabdomyolysis, and hypoxia. Current guidelines recommend the use of penicillin, as well as other antibiotics, including Ceftriaxone or Cefotaxime. Treatment of leptospiral AKI is a crucial part of the clinical support. There is evidence of clinical benefits of early renal replacement therapy in leptospirosis.