This report describes the assessment of the homology-based predictions submitted to the fifth edition of the Critical Assessment of Methods for Protein Structure Prediction (CASP5) experiment. We assessed the ability of the methods to predict the overall fold, the portions of the structure that differ substantially between the target protein and its closest structural homologue and the conformation of the side-chains. We also compared the results with those obtained in previous editions of the experiment and derived some general conclusions about the state of the art of comparative modeling methods and their usefulness for experimentalists. Proteins 2003;53:352–368. © 2003 Wiley-Liss, Inc.