Over the past 30 years, a number of therapeutic agents have been introduced for the treatment of virus diseases. Idoxuridine, a fairly nonselective drug, was developed in the 1960s for the topical treatment of HSV keratoconjunctivitis and demonstrated for the first time that virus infections were treatable. This was followed by several other anti-herpes nucleoside analogues, but the 1980s saw the first truly selective and specific inhibitor of virus replication, aciclovir. This compound is used in the treatment of herpesvirus infections, and it has taught us much about how these infections should be managed. As the mechanisms of action of drugs like aciclovir and a variety of other nucleoside analogues were identified, drugs were successfully developed and employed for the treatment of a variety of viral infections, including diseases caused by herpes simplex virus, varicella zoster virus, respiratory syncytial virus, influenza, human immunodeficiency virus, human papilloma virus infections, and hepatitis B and C. These successful developments in antiviral therapy were paralleled by an enhanced understanding of the natural history and pathogenesis of viral disease. Future developments in antiviral treatment will require the application of lessons from the past to new drug development, including the requirement for enhanced penetration across the blood-brain barrier, selectivity, oral availability, and optimal cost. Awareness of the development of antiviral resistance and its implications for antiviral drug development will be important in future developments in antiviral therapy. The review concludes by considering future clinical needs in the light of experience to date, and the molecular targets which may be amenable to therapeutic attack and thus help satisfy those needs.