Silicon, the element most similar to carbon, differs from carbon by its inability to form strong double bonds. Silanediols are therefore analogous to stable, hydrated carbonyls. We have prepared and evaluated three structures as nonhydrolyzable dipeptide analogues. In each case, derivatives of these central components provided low nanomolar inhibition of metallo- and aspartic proteases. Advances in efficient methods for their asymmetric synthesis now makes these silanediols readily accessible. Application of silanediol inhibitors to the inhibition of serine proteases will also be discussed.