Microbes have evolved a variety of strategies to survive inside their host cells. Some have the molecular machinery to survive in the hostile environment of phagolysosomes; others escape the phagosome to the more cozy environment of the cell cytoplasm; others inhibit the phagosome fusion with hydrolase-enriched endocytic organelles. This is the case for the promastigote form of the protozoan parasite Leishmania donovani which resides in a phagosome displaying poor fusogenic properties towards endosomes and lysosomes. Recent results indicate that the lipophosphoglycan (LPG), the major cell surface molecule of Leishmania, is involved in the inhibition of phagosome maturation. Further studies in our laboratories are addressing the molecular mechanisms of action of LPG to modulate phagosome fusion properties and its effect on the biogenesis of phagolysosomes.