Establishment of selective antiviral chemotherapy has achieved dramatic improvement of the prognosis of several viral infections. It has been considered for a long time that, unlike bacterial infections, viral diseases cannot be successfully treated with chemotherapeutic agents, since viral replication mostly depends on the host-cellular machinery. In fact, some compounds were reported to inhibit viral replication even in the 1950s and 1960s, yet they were also quite toxic to the host cells. The first antiviral compound that strongly inhibits viral replication without affecting the uninfected cells is the anti-herpes agent acyclovir (ACV), which was discovered in the 1970s. Furthermore, in the 1980s, the world-wide epidemic of AIDS caused by human immunodeficiency virus type 1 (HIV-1) infection has dramatically accelerated the development of new antiviral agents. At present, most of the effective antivirals are targeted at virus-specific enzymes, such as ACV for herpes virus thymidine kinase, zidovudine for HIV-1 reverse transcriptase, squinavir for HIV-1 protease, and oseltamivir for neuraminidase of influenza virus. These agents can be administered systemically without serious side effects. However, several drawbacks, including delayed toxicity and drug-resistance, are associated with long-term treatment with several antiviral agents mostly in highly active antiretroviral therapy for HIV-1 infection. Thus, it seems still mandatory to continue the search for more effective and less toxic compounds against various viral infections.