Protozoan parasites of the Leishmania genus are the causative agents of important diseases in humans and animals. During their life cycle in vertebrate hosts, protozoa are able to live and proliferate within phagolysosomes of host phagocytic cells. The capacity to live in this hostile environment is likely due to the cell surface glycoconjugate expression. In particular, lipophosphoglycan (LPG), a major surface glycoconjugate of Leishmania promastigotes, has been reported to play an active role in protecting parasites within phagolysosomes via the impairment of killing mechanisms. In this review, the authors emphasize some novel LPG-mediated escape mechanisms of promastigotes from human phagocyte responses, such as the impairment of oxidative burst and of chemotactic activity. In the light of these findings, the knowledge of biological actions of LPG may be useful in order to prepare a vaccine against human leishmaniasis, using LPG defective avirulent mutant strains.