There are many factors that can influence the efficacy of drugs in the trea
tment of leishmaniasis. These include both an intrinsic variation in the se
nsitivity of Leishmania species, described for pentavalent antimonials, par
omomycin, azoles and other drugs that have reached clinical trials, as well
as acquired drug resistance to antimonials. Acquired resistance has been s
tudied in the laboratory for several decades but it is only recently that c
linical resistance in L. donovani field isolates has been demonstrated. The
monitoring of resistance is problematic due to a reliance on the amastigot
e-macrophage culture assay to adequately correlate clinical and in vitro re
sistance and a lack of knowledge about the molecular and biochemical mechan
isms of resistance to antileishmanial drugs.