The recruitment of mRNA onto the ribosome affects not only global translation but also the spatial and temporal fine-tuning of eukaryotic translation initiation. The eukaryotic initiation factor 4 (eIF4) factors, namely, eIF4G, eIF4E, eIF4A, and eIF4B, facilitate the recruitment of mRNA onto the preassembled 43S pre-initiation complex (PIC), thus leading to the formation of the 48S PIC. Several biochemical and genetic studies have established the roles of eIF4 factors; however, the available structural information is limited. While structures of some of the individual components and subcomplexes are available, the structural details of activated mRNA bound to eIF4 factors (eIF4-mRNA) are missing. Structural characterization of the eIF4-mRNA in association with the 43S PIC in different organisms is crucial for a detailed understanding of mRNA recruitment and for exploiting the structural differences for possible drug design.