Arthropods in at least 23 different families or orders, distributed between two classes (Insecta and Arachnida), feed on vertebrate blood. They are able to do this despite constraints imposed by a sophisticated array of hemostatic defenses, due to the presence of a wide range of antihemostatic molecules in their saliva, including vasodilators, antiplatelet factors, and anticoagulants. Vasodilators include amines, prostaglandins, peptides, proteins, and even a mechanism to store large amounts of nitric oxide and deliver it into the skin. Platelet aggregation inhibitors include nitric oxide, prostaglandins, apyrase, molecules that sequester ADP, and a range of peptides and proteins that interact specifically with integrin receptors. Anticoagulants include a wide variety of inhibitors that target thrombin and factor Xa, as well as proteins that disrupt the “tenase”, prothrombinase, and tissue factor / FVIIa complexes. The potential complexity of saliva is illustrated with the example of Rhodnius prolixus, which contains a large array of compounds, many of which affect more than one target in the hem ostatic process. Finally a brief discussion of a new approach (sialomics) to the discovery of pharmacological agents in arthropod saliva is presented.