Leishmania-sand fly interactions are reviewed in the context of the potential barriers to the complete development of the parasite that exist within the midgut environment of phlebotomine flies and the molecular adaptations that the parasite has evolved that permit the development of transmissible infections to proceed. Cell surface and secreted phosphoglycans protect the parasite from the proteolytic activities of the blood-fed midgut, mediate attachment to the gut wall in order to maintain infection during excretion of the bloodmeal, and contribute to the formation of a biological plug in the anterior gut that may promote transmission by bite. The importance of vector saliva in modulating the host response to transmitted parasites is also reviewed.