Traditional small-molecule antiviral agents inhibit enzymes that are important to viral replication or reverse transcription. The synthesis and design of nucleoside-based antiviral agents is well-established and many clinically important drugs have been developed (e.g. acyclovir and AZT). However, it has proved difficult to develop compounds with the ability to eliminate viruses entirely or to prevent their integration into the host genome. For this reason a number of oligonucleotide-based approaches are now being developed. This document gives an overview of the current and future use of oligonucleotides as drug molecules.