Peptide-bond formation is the enzymatic activity of the ribosome. The catalytic site is made up of ribosomal RNA, indicating that the ribosome is a ribozyme. This review summarizes the recent progress in understanding the mechanism of peptide bond formation. The results of biochemical and kinetic experiments, mutagenesis studies and ribosome crystallography suggest that the approx. 10(7)-fold rate enhancement of peptide bond formation by the ribosome is mainly due to substrate positioning within the active site, rather than to chemical catalysis.