The proteasome is the main ATP-dependent protease in eukaryotic cells and controls the concentration of many regulatory proteins. Protein unfolding is a key step in degradation and the proteasome can actively unfold its substrates.  By mutating substrate proteins systematically, we found that the proteasome catalyzes unfolding by unravelling its substrates processively from their degradation signal.  Because of this mechanism, the susceptibility of a protein to degradation depends on the local structure first encountered by the protease.  We will discuss how the unfolding step contributes to substrate selection by the proteasome and to the structure of the degradation end product.