Although, in southern Europe, there has been considerable experience in the treatment of visceral leishmaniasis (VL) in HIV-positive patients, the optimal therapy has yet to be established. Pentavalent antimony salts, free amphotericin B deoxycholate (ABD) and lipidic formulations of amphotericin B are the drugs most commonly used. Treatment with pentavalent antimonials requires daily injections for 28 days, is not well tolerated and leads to initial clinical cure in only 66% of the co-infected cases. Free ABD has to be given, intravenously, for just as long, has significant toxicity and leads to initial clinical cure in even fewer cases (62%). In a prospective, comparative trial, treatment of co-infected cases with a pentavalent antimonial was found to have similar efficacy and toxicity to treatment with free ABD. The duration of treatment and the associated toxicity may both be reduced by the use of lipidic formulations of amphotericin B. Anecdotal evidence and the results of non-randomized trials indicate that treatment with liposomal amphotericin B is highly effective. In a comparative trial, amphotericin B lipid complex was found to be not only as effective as a pentavalent antimonial but also better tolerated. At the moment, however, such lipidic formulations have only been tested against VL/HIV cases in Europe, not elsewhere in the world, and they remain very expensive. However successful the treatment in terms of initial clinical cure, almost all VL/HIV cases develop VL relapses. Although the data available on secondary prophylaxis are limited and often inconclusive, it appears that regular treatment with a pentavalent antimonial drug, liposomal amphothericin B or amphotericin B lipid complex can reduce the incidence of leishmanial relapses in HIV-positive patients with VL. The development of new regimens, use of new oral drugs (such as miltefosine) and the development of new antileishmanial drugs could all improve the treatment of HIV-related VL in the future.