Bunyaviricetes represents a diverse class of RNA viruses, including hundreds of species distributed worldwide that threaten human and animal health. This Perspective briefly overviews bunyaviruses infecting humans and other mammals, focusing on their key virulence factor, the nonstructural protein NSs. By subverting host cell processes, NSs promotes immune evasion and viral replication. Here, we discuss its role in bunyavirus cytotoxicity and virulence and highlight its implications for pathogenesis.