Tears are highly concentrated in proteins relative to other biofluids, and a 
notable fraction of tear proteins are proteases and protease inhibitors. These 
components are present in a delicate equilibrium that maintains ocular surface 
homeostasis in response to physiological and temporal cues. Dysregulation of the 
activity of protease and protease inhibitors in tears occurs in ocular surface 
diseases including dry eye and infection, and ocular surface conditions 
including wound healing after refractive surgery and contact lens (CL) wear. 
Measurement of these changes can provide general information regarding ocular 
surface health and, increasingly, has the potential to give specific clues 
regarding disease diagnosis and guidance for treatment. Here, we review three 
major categories of tear proteases (matrix metalloproteinases, cathepsins, and 
plasminogen activators [PAs]) and their endogenous inhibitors (tissue inhibitors 
of metalloproteinases, cystatins, and PA inhibitors), and the changes in these 
factors associated with dry eye, infection and allergy, refractive surgery, and 
CLs. We highlight suggestions for development of these and other 
protease/protease inhibitor biomarkers in this promising field.