Ribosomes that translate mRNAs lacking stop codons become stalled at the 3′ end of the mRNA. Recycling of these stalled ribosomes is essential for cell viability. In bacteria three ribosome rescue systems have been identified so far, with the most ubiquitous and best characterized being the trans-translation system mediated by transfer–messenger RNA (tmRNA) and small protein B (SmpB). The two additional rescue systems present in some bacteria employ alternative rescue factor (Arf) A and release factor (RF) 2 or ArfB. Recent structures have revealed how ArfA mediates ribosome rescue by recruiting the canonical termination factor RF2 to ribosomes stalled on truncated mRNAs. This now provides us with the opportunity to compare and contrast the available structures of all three bacterial ribosome rescue systems. Bacterial ribosome rescue systems are ubiquitous in bacteria and essential for cell viability. Homologs of some rescue factors are also found in eukaryotic mitochondria and plant chloroplasts. Bacterial ribosome rescue factors such as small protein B (SmpB), alternative rescue factor (Arf) A, and ArfB recognize ribosomes stalled on truncated mRNAs by using their positively charged C-terminal tails to probe whether the mRNA channel is vacant. ArfA induces conformational changes within the 'switch’ loop of release factor 2 (RF2) that promotes transition from a closed to an open conformation, placing the catalytically important glycine–glycine–glutamine (GGQ) motif of RF2 at the peptidyltransferase center of the ribosome. The distinct pathways used to rescue bacterial and eukaryotic cytoplasmic non-stop ribosome complexes suggest that bacterial ribosome rescue may be a potential target for the development of new antimicrobial agents.