Viral diseases are one of the leading causes of morbidity and mortality in the world. Broad-spectrum antiviral agents (BSAAs) are key players in control of human viral diseases. Here, we reviewed the discovery and development process of BSAAs, focusing on compounds with available safety profiles in human. In addition, we summarized the information on approved, investigational and experimental safe-in-man BSAAs in freely accessible database at https://drugvirus.info/. The number of approved BSAAs will be increased as well as their spectrum of indications will be expanded pending the results of further pre-clinical and clinical studies. This will ultimately reinforce the arsenal of available antiviral options and provide better protection of general population from emerging and re-emerging viral diseases.