Since Fleming's discovery of penicillin in 1928, the treatment of bacterial infections has undergone extraordinary advances. More recently, antiviral treatment has experienced a comparable scientific revolution. Although clinicians' knowledge and abilities to battle viruses on a biochemical level are limited, new progress in this field is occurring steadily at a rapid pace. The overall intent of this article is to equip the practicing clinician with information regarding systemic antiviral agents used in dermatology, with particular focus on the specific treatments for herpes simplex virus (HSV) and varicella-zoster virus (VZV) infections. The antiviral drugs indicated for chronic viral hepatitis, cytomegalovirus (CMV), and human immunodeficiency virus (HIV) are discussed because the dermatologist may be involved with the care of patients with these infections. The discussion of topical antiviral agents, immunotherapy, and vaccinations is beyond the scope of this article.