Leishmaniasis, a disease of global relevance, results from infection with the protozoan parasite, , which is transmitted to susceptible hosts through the bite of sand flies. Multiple forms of leishmaniasis may occur, including cutaneous, mucocutaneous, and visceral. Research with animal models remains an important approach to help define basic pathophysi- ologic processes associated with infection and disease. In this regard, mice and hamsters represent the most commonly used models. The severity of leishmaniasis in animal models depends on several factors, including genotype of the host and parasite and the dose and route of administration of the parasite to the host, and severity of outcome may range from subclinical to severe illness. This review provides basic background on leishmaniasis, relevant animal models, the pathophysiology and clinical signs in animals used as models of leishmaniasis, and general approaches to mitigate risk to personnel.