Considering the serious economic problems caused by plant viruses, the development of virus-resistant plants is highly critical in plant breeding. The disease arises from a compatible interaction between the plant and the pathogen. Plant viruses, which are obligatory intracellular parasites, are closely associated with the cellular environment of the host plant and are entirely dependent on it. This dependence requires viral nucleic acids and proteins to deprive plant resources, including host factors, from their normal function. Plant viruses not only utilize plant translation factors for the translation of their viral RNAs but also manipulate these factors for their replication. Additionally, plant translation factors contribute to the local and systemic movements of viruses. The dependence of viruses on the host factors of the plant explains the association of mutations in genes belonging to the translation initiation factor eIF4 gene family, including many naturally occurring recessive resistance genes identified in plants. Specific mutations or suppression of these genes provide resistance against viruses without compromising plant health. Understanding the mechanisms that control the development of natural resistance against plant viruses and the emergence of virulent isolates in response to this resistance will be beneficial in the selection of new sources of broad-spectrum and durable resistance.