Soon aft er discovery of RNA interference (RNAi), its potential as eff ective antiviral therapy was recognized. Since then RNAi has been variously exploited for antiviral purposes which could eff ectively block viral replication in vitro. For invivo use, however, delivery issue, toxicity, RNAi suppression and viral escape are still major hurdles. Here, we providean overview of the RNAi strategy and review the approaches that have been developed to surpass the obstacles and to achieve targeted gene silencing for antiviral and other therapies.