A decade ago, just five drugs were licensed for the treatment of viral infections. Since then, greater understanding of viral life cycles, prompted in particular by the need to combat human immunodeficiency virus, has resulted in the discovery and validation of several targets for therapeutic intervention. Consequently, the current antiviral repertoire now includes more than 30 drugs. But we still lack effective therapies for several viral infections, and established treatments are not always effective or well tolerated, highlighting the need for further refinement of antiviral drug design and development. Here, I describe the rationale behind current and future drug-based strategies for combating viral infections.