The life cycle of Leishmania in the sand fly consists of a complex sequence of events in which the parasites transform from intracellular amastigotes to infective promastigotes. One of the major obstacles to be overcome to insure the survival of the parasites is binding to the midgut epithelium of sand flies to avoid expulsion with bloodmeal remnants. Lipophosphoglycan (LPG), an abundant surface molecule on promastigotes, was shown to be the major ligand required for midgut attachment. LPG is highly polymorphic among different Leishmania species, most likely a reflection of the complexity of the vector’s midgut receptor. In some sand fly vectors, a strict species-specific vector competence exists where a fly species is only able to support the development of a single Leishmania species. Other sand flies seem to be more “permissive” allowing for the survival and complete development of different Leishmania species. PpGalec, a tandem repeat galectin, was identified from the sand fly P. papatasi, a sand fly species that only permits the growth of L. major parasites. This is the first sand fly midgut receptor characterized to date. Thus, blocking midgut receptors may be a promising transmission blocking strategy. The search for midgut receptors in other flies is ongoing.