Recognition of the mRNA cap structure by the translation initiation factor eIF4E is central to protein synthesis in general and eIF4E activity is especially important for the production of many of the proteins that give rise to the hallmarks of cancer. Because transformed cells have a heightened requirement for the expression of prosurvival factors, targeting translation appears to be an attractive anticancer strategy and proof-of-concept studies in which oncogenic eIF4E function is suppressed in various different ways show that tumour cells are selectively sensitive to inhibition of protein synthesis at the level of eIF4E. The emerging understanding of the functions, regulation, and structural biology of eIF4E now makes possible the pharmacological targeting of this key translation initiation factor.