Publisher Summary This chater discusses the agents with activity against RNA viruses. The primary problem confronting those who would develop safe and efficacious drugs to treat virus diseases is the necessity to selectively inhibit the apparently few biochemical functions that are uniquely utilized by viruses. Because the replication of viruses requires the use of so many host cellular functions, severe drug-induced toxicity occurs in the host if the viral functions are not blocked selectively. Among a series of sulfonylthiourea analogs of amantadine, such a particular compound exhibited strong anti-influenza virus activity both in vitro and in vivo. The activity compared closely with that of amantadine that was tested in parallel. R-avirin and the related formycin A and B are known to inhibit RNA viruses to varying degrees. As with other nucleosides, 6-azauridine must be converted to a nucleotide to be active. 6-azauridine is phosphorylated by uridine kinase to the 5’ monophosphate that acts as a competitive inhibitor of monophosorotidylate (OMP) decarboxylase. The antiviral activity of the compound has been explored in several animal models and in humans. Despite the fact that 6-azauridine was not highly active against pox and herpesviruses in vitro, most experimental animal and human studies have concentrated on these DNA viruses.