This article is an introduction to the special issue of the journal Proteins, dedicated to the sixth CASP experiment to assess the state of the art in protein structure prediction. The article describes the conduct of the experiment and the categories of prediction included, and outlines the evaluation and assessment procedures. A brief summary of progress over the decade of CASP experiments is also provided. Proteins 2005;Suppl 7:3–7. © 2005 Wiley-Liss, Inc.