The article discusses the significance and mechanisms of codon bias, which refers to the non-uniform use of different codons for the same amino acid in genes. Despite being synonymous, these mutations have substantial effects on cellular processes and are crucial in molecular evolution and biotechnology. Recent advances in sequencing and synthetic biology have helped resolve long-standing questions about codon bias and uncovered new patterns that suggest new hypotheses about protein synthesis. The dynamics of initiation and elongation are key to understanding natural synonymous variation and designing transgenes. The authors review the causes and consequences of codon bias, focusing on classical hypotheses and recent developments from high-throughput studies. They highlight the strong correlation between codon usage and gene expression levels, suggesting that codon bias is more extreme in highly expressed genes to match the skew in iso-accepting tRNAs and enhance translation efficiency or accuracy. They also discuss the role of mRNA structure, ribosomal pausing, and tRNA recycling in shaping codon usage. In applied settings, codon optimization has traditionally focused on matching cellular tRNA abundances, but recent studies advocate for considering global nucleotide content, local mRNA folding, codon pair bias, and codon correlations. The effects of codon adaptation on expression levels are mixed, with some studies showing increased expression and others finding no significant correlation. The article concludes by emphasizing the need for cross-fertilization between biotechnological and molecular biological studies to elucidate effective strategies for designing transgenes and understand the underlying mechanisms of their expression.The article discusses the significance and mechanisms of codon bias, which refers to the non-uniform use of different codons for the same amino acid in genes. Despite being synonymous, these mutations have substantial effects on cellular processes and are crucial in molecular evolution and biotechnology. Recent advances in sequencing and synthetic biology have helped resolve long-standing questions about codon bias and uncovered new patterns that suggest new hypotheses about protein synthesis. The dynamics of initiation and elongation are key to understanding natural synonymous variation and designing transgenes. The authors review the causes and consequences of codon bias, focusing on classical hypotheses and recent developments from high-throughput studies. They highlight the strong correlation between codon usage and gene expression levels, suggesting that codon bias is more extreme in highly expressed genes to match the skew in iso-accepting tRNAs and enhance translation efficiency or accuracy. They also discuss the role of mRNA structure, ribosomal pausing, and tRNA recycling in shaping codon usage. In applied settings, codon optimization has traditionally focused on matching cellular tRNA abundances, but recent studies advocate for considering global nucleotide content, local mRNA folding, codon pair bias, and codon correlations. The effects of codon adaptation on expression levels are mixed, with some studies showing increased expression and others finding no significant correlation. The article concludes by emphasizing the need for cross-fertilization between biotechnological and molecular biological studies to elucidate effective strategies for designing transgenes and understand the underlying mechanisms of their expression.