Smallpox (variola major), and the haemorrhagic fever viruses (filoviruses and arenaviruses) are classified as Category A biowarfare agents by the Centers for Disease Control. Category A agents pose a significant risk to public health and national security because they can be easily disseminated by aerosol, although with the exception of variola, they are not easily transmitted from person to person. An attack with these viruses would result in high morbidity and mortality and cause widespread panic. With the exception of smallpox and Argentine haemorrhagic fever virus, there are no vaccines or approved treatments to protect against these diseases. In this review we focus on promising prophylactic, therapeutic and disease modulating drugs (see Figure 1 for select chemical structures).