Translation initiation is a crucial step of protein synthesis which largely defines how the composition of the cellular transcriptome is converted to the proteome and controls the response and adaptation to environmental stimuli. The efficiency of translation of individual mRNAs, and hence the basal shape of the proteome, is defined by the structures of the mRNA translation initiation regions. Initiation efficiency can be regulated by small molecules, proteins, or antisense RNAs, underscoring its importance in translational control. Although initiation has been studied in bacteria for decades, many aspects remain poorly understood. Recent evidence has suggested an unexpected diversity of pathways by which mRNAs can be recruited to the bacterial ribosome, the importance of structural dynamics of initiation intermediates, and the complexity of checkpoints for mRNA selection. In this review, we discuss how the ribosome shapes the landscape of translation initiation by non-linear kinetic processing of the transcriptome information. We summarize the major pathways by which mRNAs enter the ribosome depending on the structure of their 5′ untranslated regions, the assembly and the structure of initiation intermediates, the individual and synergistic roles of initiation factors, and the mechanisms of mRNA and initiator tRNA selection. © 2012 Informa Healthcare USA, Inc.