Since the release of amantadine in 1966, other agents designed to fight a diverse range of viral infections have been released. Part I of this two-part article focuses on agents used to manage hepatitis, cytomegalovirus, and herpes infections. In patients with chronic hepatitis B, interferon alfa-2b or lamivudine is the treatment of choice. Pegylated interferon alfa-2a or -2b, along with ribavirin, is standard treatment for patients with chronic hepatitis C. Although treatment of cytomegalovirus infections generally is supportive, there have been reports of severely ill patients who improved after receiving ganciclovir or foscarnet. Oral antiviral agents for initial and recurrent herpes simplex virus infections have been shown to shorten the duration of lesions. Treatment of herpes zoster infections with antiviral drugs shortens the course of infection and decreases symptoms. Studies have shown that antiviral treatment can prevent prolonged post-herpetic neuralgia, although this use remains controversial.