Within the Diptera and outside the suborder Brachycera, the blood feeding habit occurred at least
twice, producing the present day sand flies, and the Culicomorpha, including the mosquitoes (Culicidae),
black flies (Simulidae), biting midges (Ceratopogonidae) and frog feeding flies (Corethrellidae).
Alternatives to this scenario are also discussed. Successful blood feeding requires adaptations to
antagonize the vertebrate’s mechanisms of blood clotting, platelet aggregation, vasoconstriction, pain and
itching, which are triggered by tissue destruction and immune reactions to insect products. Saliva of these
insects provides a complex pharmacological armamentarium to block these vertebrate reactions. With the
advent of transcriptomics, the sialomes (from the Greek word sialo=saliva) of at least two species of each
of these families have been studied (except for the frog feeders), allowing an insight into the diverse
pathways leading to today’s salivary composition within the Culicomorpha, having the sand flies as an
outgroup. This review catalogs 1,288 salivary proteins in 10 generic classes comprising over 150 different
protein families, most of which we have no functional knowledge. These proteins and many sequence
comparisons are displayed in a hyperlinked spreadsheet that hopefully will stimulate and facilitate the
task of functional characterization of these proteins, and their possible use as novel pharmacological
agents and epidemiological markers of insect vector exposure.