The 5' untranslated region (5'UTR) of eukaryotic mRNAs plays a crucial role in ribosome recruitment and start codon selection, significantly influencing translation efficiency and the cellular proteome. The ribosomal initiation complex assembles via cap-dependent or cap-independent mechanisms, facilitated by various factors and structures within the 5'UTR. Key mechanisms include the scanning mechanism, where the PIC scans the mRNA for an AUG start codon, and the role of internal ribosome entry sites (IRESs) in recruiting PICs to specific sequences in the 5'UTR. The Kozak consensus sequence is essential for optimal AUG recognition, and leaky scanning allows the use of alternative start codons. The 5'UTR's secondary structures can influence start codon selection and translation efficiency, with DEAD-box ATPases and eIF4A playing important roles in resolving these structures. Upstream open reading frames (uORFs) can regulate translation by stalling ribosomes or enabling leaky scanning, and their presence can be modulated by posttranslational modifications and small molecules. The 5'UTR also contains regulatory elements like the 5'TOP motif and m6A methylation, which affect translation initiation. Viral mRNAs often use IRES elements to bypass the scanning process, and cellular mRNAs may also contain IRESs. Advances in techniques such as ribosome profiling and cryo-electron microscopy are expected to further our understanding of these mechanisms and aid in the development of new drugs for diseases associated with dysregulated translation.The 5' untranslated region (5'UTR) of eukaryotic mRNAs plays a crucial role in ribosome recruitment and start codon selection, significantly influencing translation efficiency and the cellular proteome. The ribosomal initiation complex assembles via cap-dependent or cap-independent mechanisms, facilitated by various factors and structures within the 5'UTR. Key mechanisms include the scanning mechanism, where the PIC scans the mRNA for an AUG start codon, and the role of internal ribosome entry sites (IRESs) in recruiting PICs to specific sequences in the 5'UTR. The Kozak consensus sequence is essential for optimal AUG recognition, and leaky scanning allows the use of alternative start codons. The 5'UTR's secondary structures can influence start codon selection and translation efficiency, with DEAD-box ATPases and eIF4A playing important roles in resolving these structures. Upstream open reading frames (uORFs) can regulate translation by stalling ribosomes or enabling leaky scanning, and their presence can be modulated by posttranslational modifications and small molecules. The 5'UTR also contains regulatory elements like the 5'TOP motif and m6A methylation, which affect translation initiation. Viral mRNAs often use IRES elements to bypass the scanning process, and cellular mRNAs may also contain IRESs. Advances in techniques such as ribosome profiling and cryo-electron microscopy are expected to further our understanding of these mechanisms and aid in the development of new drugs for diseases associated with dysregulated translation.