OBJECTIVE: To alert clinicians to the climatic conditions that can precipitate outbreaks of the rodent-borne infectious diseases most often associated with flooding disasters, leptospirosis (LS), and the Hantavirus-caused diseases, hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS); to describe the epidemiology and presenting clinical manifestations and outcomes of these rodent-borne infectious diseases; and to recommend both prophylactic therapies and effective control and prevention strategies for rodent-borne infectious diseases. DESIGN: Internet search engines, including Google(R), Google Scholar(R), Pub Med, Medline, and Ovid, were queried with the key words as search terms to examine the latest scientific articles on rodent-borne infectious disease outbreaks in the United States and worldwide to describe the epidemiology and presenting clinical manifestations and outcomes of LS and Hantavirus outbreaks. SETTING: Not applicable. PARTICIPANTS: Not applicable. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Rodent-borne infectious disease outbreaks following heavy rainfall and flooding disasters. RESULTS: Heavy rainfall encourages excessive wild grass seed production that supports increased outdoor rodent population densities; and flooding forces rodents from their burrows near water sources into the built environment and closer to humans. CONCLUSIONS: Healthcare providers should maintain high levels of suspicion for LS in patients developing febrile illnesses after contaminated freshwater exposures following heavy rainfall, flooding, and even freshwater recreational events; and for Hantavirus-caused infectious diseases in patients with hemorrhagic fevers that progress rapidly to respiratory or renal failure following rodent exposures.