Sand fly saliva contains an array of bioactive molecules that facilitate blood feeding and also function as modulators of the vertebrate immune response. Such a complex of biologically active molecules was shown to be both conserved and divergent among sand fly species. It is likely that expression of sand fly salivary molecules could be modulated by environmental factors, both biotic and abiotic, that ultimately dictate the quality, and possibly quantity, of the secreted saliva. Carbohydrates are an integral part of the sand fly diet, and sugar-sources found in natural habitats are potentially involved in defining the profile of sand fly saliva, and may influence vectorial capacity. Saliva can drive the outcome of Leishmania infection in animal models, and salivary molecules are potential targets for development of vaccines to control Leishmania infection. Thus, identifying what environmental factors effectively modulate sand fly saliva in the field is a critical step towards the development of meaningful protection strategies against leishmaniasis that are based on salivary compounds from sand fly vectors.