Genetic resistance in host plants is one of the most effective and sustainable strategies for managing agricultural viruses. This chapter addresses the main mechanisms of antiviral resistance, from vertical defense, characterized by specificity and intensity, to polygenic and more durable resistance. Resistance mechanisms in plants, such as gene silencing by RNAi, susceptibility genes, and hormonal regulation in modulating the immune response, are also discussed. The application of biotechnological and molecular tools has expanded the possibilities for exploring these mechanisms. QTL mapping, molecular markers, and assisted selection have accelerated the identification and use of loci associated with resistance. Recent technologies, including RNA-seq, GWAS, and gene editing, broaden our understanding of the mechanisms underlying antiviral resistance and provide new opportunities for identifying target genes and developing more resilient cultivars. Despite these advances, problems persist, such as rapid viral evolution, the breakdown of resistance in cultivars, the impact of mixed infections, and technical limitations in perennial crops. Prospects include the integration of omics data, high-throughput phenotyping, and bioinformatic tools, which can increase the accuracy and reduce the costs of breeding programs. The convergence of biotechnology, classical breeding, and digital agriculture promises to strengthen plant resilience and reduce losses associated with viruses. Therefore, understanding and exploring the multiple mechanisms of resistance remains essential to promoting food security and agricultural sustainability in a scenario of increasing pressure from viral pathogens.