Salivary gland hypertrophy viruses (SGHVs) are a unique, unclassified group of entomopathogenic, double-stranded DNA viruses that have been reported from three genera of Diptera. These viruses replicate in nuclei of salivary gland cells in adult flies, inducing gland enlargement with little obvious external disease symptoms. Viral infection inhibits reproduction by suppressing vitellogenesis, causing testicular aberrations, and/or disrupting mating behavior. Historical and present research findings support a recent proposal of a new virus family, the Hytrosaviridae. This review describes the discovery and prevalence of different SGHVs, summarizes their biochemical characterization and taxonomy, compares morphological and histopathological properties, and details transmission routes and the influence of infection on host biology and reproduction. In addition, the potential use of SGHVs as sterilizing agents for house fly control and the deleterious impact of SGHVs on colonized tsetse flies reared for sterile insect technique are discussed.