Viruses represent significant threats to modern agriculture and their biological control remains a challenge in the twenty-first century. Recent progress has been made in our understanding of natural and engineered virus resistance, the two major strategies used for crop protection. The molecular mechanisms underlying the roles of both dominant and recessive resistance genes have been elucidated, promoting the development of possible new antiviral strategies. Engineering resistance in plants, in particular RNA-mediated protection, is also becoming increasingly important and is likely to play a key role in the future.