Orthopoxviruses encode numerous virulence factors. Viral inhibitors of apoptosis of infected cells have been revealed in recent years. Viral inhibitors of the host's non-specific inflammatory reactions are shown to play an important role in effectively propagating the virus. A number of inhibitors of antiviral interferon action cause a high interferon resistance of orthopoxviruses. Some modulators of immune response of the infected body encoded by orthopoxviruses have been discovered in the past years. Viral growth factor, some proteins of the envelope of extracellular virions, etc. are shown to be important for viral dissemination in the host. A general scheme of synthesis of molecular factors of orthopoxviral virulence is discussed.