CONTEXT: Visceral leishmaniasis (VL) is a severe and potentially fatal infection caused by the trypanosome parasite Leishmania sp. Over 90% of reported cases occur in India, Bangladesh, Nepal, Sudan, and Brazil, affecting mainly impoverished individuals and creating a significant economic burden through direct and indirect costs of treatment. OBJECTIVES: To identify the direct and indirect costs of VL treatment, compare these costs to household income, and identify the barriers to treatment in each of the five VL-endemic countries. METHODS: Articles obtained through PubMed (US National Library of Medicine), EMBASE, and Cochrane Library were selected for relevance to VL treatment, costs for all forms of amphotericin B, miltefosine, paromomycin, and antimony compounds, and healthcare costs in India, Bangladesh, Nepal, Brazil, and Sudan. Healthcare statistics were obtained from the World Health Organization Statistical Information System, Médecins Sans Frontieres, and each country's national health ministry. RESULTS: Per capita GDP, per capita GNI, cost of drugs, and hospitalization expenses differ by up to 10-fold in each of the five countries where VL is hyperendemic, resulting in unequal barriers to treatment. We found that the cost of specific drugs influences the choice of therapy. CONCLUSIONS: Poverty and VL treatment-related costs cause potential limitations in the provision of full and efficacious treatment, which may result in further dissemination of the disease. Effective nonparenteral antileishmania drugs would provide a significant advantage in reducing the barriers to VL treatment.