Visceral leishmaniasis presents a serious problem in endemic regions that is difficult to treat or prevent. Several epidemiologic problems make the disease particularly troublesome to manage. These include the facts that classic visceral leishmaniasis is fatal if untreated and there is not reliable access to medical care in many endemic regions. When available, treatment has associated toxicity and requires the use of intravenous medications with careful monitoring for toxicity, which are complex to administer in underdeveloped nations. There is an increasing incidence of the disease in HIV-infected individuals in southern Europe, in part because of the fact that eradication of the organism from infected persons using currently available drugs appears to be difficult if not impossible. Furthermore, chronic cutaneous forms of the disease allow humans and animals to maintain the organism long-term in a bodily site that is easily accessible to the sandfly vector. More effective and less toxic treatment modalities as well as a protective vaccine are badly needed to manage this disease.