Leishmaniasis is caused by a wide range of parasites that are transmitted by an even wider range of sand fly vectors. The phlebotomine vectors of Leishmaniasis are in some cases only permissive to the complete development of the species of Leishmania that they transmit in nature. The parasite-sand fly interactions that control this specificity are related to differences in the ability of the parasite to inhibit or to resist killing by proteolytic enzymes released into the mid-gut soon after blood feeding, and/or to maintain infection in the mid-gut during excretion of the digested blood meal. In each case, surface expressed or released phosphoglycan-containing molecules appear to promote parasite survival. The evidence that the surface lipophosphoglycan (LPG) mediates promastigote attachment to the mid-gut epithelium so as to prevent their loss during blood-meal excretion is especially strong based on the comparison of development in sand flies using LPG-deficient mutants. LPG displays interspecies polymorphisms in their phosphoglycan domains that in most cases can fully account for species-specific vector competence.