Over time the mechanistic concepts to describe the two principal chemical reactions that are catalyzed by the ribosome, peptide bond formation and peptidyl-tRNA hydrolysis, have undergone dramatic changes. While the initial models were based on a ribosomal protein-based mechanism, evidence for a direct functional contribution of ribosomal RNA for catalysis has accumulated over the past years. The presentation of high resolution crystallographic structures of the large ribosomal subunit at the beginning of the new millennium dramatically increased our molecular insight into the organization of the active center and finally placed the ribosome amongst the list of RNA enzymes. Combined with elaborate biochemical and biophysical approaches the translation field has made significant progress in understanding mechanistic details of ribosomal catalysis. While it seems that the mechanism of ribosome-catalyzed peptidyl-tRNA hydrolysis is just emerging, the knowledge on transpeptidation is already very advanced. It has been realized that intricate interactions between ribosomal RNA and the transfer RNA substrate are crucial for proton shuttling that is required for efficient amide bond formation.