The coding strategies of arenaviruses (family Arenaviridae) and members of the Phlebovirus genus of the Bunyaviridae differ from those of other negative-sense RNA viruses in that some proteins are coded in viral-complementary RNA sequences and others are coded in the viral RNA sequence. The term ambisense RNA has been proposed to denote these unique coding arrangements. The implications of the ambisense RNA coding strategy for the evolution and infection processes of these viruses are discussed.