Each peptide bond of a protein is generated at the peptidyl transferase center (PTC) of the ribosome and then moves through the exit tunnel, which accommodates ever-changing segments of ≈ 40 amino acids of newly translated polypeptide. A class of proteins, called ribosome arrest peptides, contains specific sequences of amino acids (arrest sequences) that interact with distinct components of the PTC-exit tunnel region of the ribosome and arrest their own translation continuation, often in a manner regulated by environmental cues. Thus, the ribosome that has translated an arrest sequence is inactivated for peptidyl transfer, translocation, or termination. The stalled ribosome then changes the configuration or localization of mRNA, resulting in specific biological outputs, including regulation of the target gene expression and downstream events of mRNA/polypeptide maturation or localization. Living organisms thus seem to have integrated potentially harmful arrest sequences into elaborate regulatory mechanisms to express genetic information in productive directions.