Blood-feeding arthropods have in their saliva a variety of molecules that affect the vertebrate host's hemostatic, inflammatory, and immune systems. The saliva of blood feeders also helps to facilitate infection of the pathogens they carry to the host, making vector saliva an attractive target to control pathogen transmission. The isolation and identification of salivary molecules from vectors of disease has been slow and difficult. Emerging technologies and new approaches in the fields of molecular biology and protein chemistry are facilitating this work. Massive sequencing of high quality, full-length cDNA libraries, coupled with proteomics and functional genomic approaches has led to the discovery of novel proteins, transcription products (genes), and biologic activities from the salivary glands of blood-feeding arthropods. This review focuses on the biologic activities identified in the saliva of various vectors of disease using classic biochemical and molecular biology approaches and new types of molecules and activities identified with high-throughput strategies.