Since 1989, Médecins Sans Frontières (MSF) has provided medical humanitarian assistance during outbreaks of visceral leishmaniasis (VL; kala-azar) in Sudan. First, in western Upper Nile in southern Sudan, where a VL epidemic occurred after the resumption of the civil war in Sudan in 1983, with an estimated 100,000 deaths. Later, MSF started interventions in eastern Upper Nile and Gedaref State. In these two endemic regions VL incidence has risen markedly since 2001, which could be the start of a new epidemic cycle. Outbreaks of VL in Sudan remain unpredictable, and access to affected populations in war-torn southern Sudan is often hampered by insecurity. Therefore, MSF takes a flexible approach, establishing treatment centres where patients can be accessed. From 1989 to 2002, MSF treated >51,000 VL cases in Sudan. Despite very basic field conditions, high cure rates of 95% are being achieved. Lack of diagnostics is a major obstacle to treatment, especially during epidemic situations. Therefore, development of simple and rapid technologies is required, allowing reliable diagnosis under field conditions. For treatment of VL there is a limited choice of effective, affordable drugs. There are strong indications of an emerging resistance to antimonials in Malakal. Introduction of combination therapies is urgently needed to prevent the further emergence and spread of resistance to antimonials, which are still the mainstay of VL treatment in eastern Africa. Experience with combination therapy with sodium stibogluconate (SSG) and paromomycin is promising, and combinations of SSg with liposomal amphotericin B and miltefosine are currently being explored.