Proteases are a class of proteins that degrade other proteins. There are several classes of proteases and these are defined by the chemical nature of the catalytic sites. The process of proteolysis is a vital function that is exquisitely regulated. Many diseases involve deregulation of proteolysis due to over-expression of one or more proteases or endogenous protease inhibitors being faulty or missing. Engineered protease inhibitors that control proteolysis are a well recognized class of therapeutics. For certain classes of proteases, small molecule inhibitors have been very successful (Threonine, Cysteine, and Aspartate proteases). For Serine and Zinc proteases, there has been little success with small molecules. Kunitz domains are natural inhibitors of Serine proteases. Using phage display, Kunitz domains can be engineered rapidly to have very high affinity and specificity for a particular serine protease. One of these, DX-88, is a potent, specific inhibitor of human plasma kallikrein and has successfully completed two phase 3 trials for hereditary angioedema, for which a BLA has been filed to the FDA, and is currently in phase 2 for reduction of blood loss in thoracic surgery. For metalloproteases, potent, specific inhibitory antibodies against several MMPs have been discovered also by phage display.