Identifying and targeting specific oncogenes, with the hope that the resultant therapies may eventually prove to exert positive clinical effects, is a major effort in the area of cancer therapeutics. The eukaryotic translation initiation factor, eIF4E, is overexpressed in many cancers, including acute myeloid leukemia. The role of eIF4E in oncogenic transformation and the development of a means to directly target its activity with ribavirin are discussed here. Results from early stage clinical trials and factors contributing to the development of clinical resistance to ribavirin are also described.