RNA interference (RNAi) is a natural mechanism in cells that suppresses or silences the expression of aberrant or foreign genes. This activity is being developed as a potential antiviral therapeutic strategy. Studies in vitro, and some in vivo, appear to show the feasibility of using RNAi to treat virus infection. Therapeutic use of RNAi seems to be promising when directed against viruses that cause localized acute infections in accessible target cells. Therapeutic strategies using RNAi against viruses that cause chronic infections, such as HIV, hepatitis B virus, or hepatitis C virus, are more difficult to design, but studies have begun to address identifiable problems. Two clinical trials using RNAi have recently been initiated--one phase II trial against respiratory syncytial virus and a phase I trial against HIV. It will be of much interest to see whether nucleic acid therapies can offer another route to treating viral infection.