In recent years, biotechnology has permitted regulation of the expression of endogenous plant genes to improve agronomicaiiy important traits. Genetic modification of crops has benefited from emerging knowledge of new genes, especially genes that exhibit novel functions, one of which is eukaryotic initiation factor 4E (elF4E). elF4E is one of the most important translation initiation factors involved in eukaryotic initiation. Recent research has demonstrated that virus resistance mediated by elF4E and its isoform elF (iso)4E occurs in several plant-virus interactions, thus indicating a potential new role for elF4E/elL(iso)4E in resistance strategies against plant viruses. In this review, we briefly describe elF4E activity in plant translation, its potential role, and functions of the elF4E subfamily in plant-virus interactions. Other initiation factors such as elF4G could also play a role in plant resistance against viruses. Finally, the potential for developing elF4E-medlated resistance to plant viruses in the future is discussed. Future research should focus on elucidation of the resistance mechanism and spectrum mediated by elF4E. Knowledge of a particular plant-virus interaction will help to deepen our understanding of elF4E and other eukaryotic initiation factors, and their involvement in virus disease control.