The TIM-barrel fold has now been found in 19 enzymes with different catalytic functions and different lengths of polypeptide chains. The domain organization of these chains are compared and discussed. For several of these chains, X-ray structures have recently been refined and active-site residues have been identified by studies of inhibitor complexes. Evolutionary implications of these results, including the first examples of evolutionarily related enzymes that catalyze different chemical reactions, are discussed.