Proteomics is an approach to looking at the identity, amount, proteolysis, compartmentalization, and posttranslational modification of a large number of proteins simultaneously in a cell or tissue. Recently, proteomics has begun to be applied to the study of pancreatitis to ascertain mechanisms of disease and search for biomarkers of disease. Most mechanistic work has been carried out in animal models of acute pancreatitis. In 8 studies, 97 proteins have been reported to increase, 55 to decrease, and 23 to undergo proteolysis. Proteins showing increases are most often related to stress, inflammation, or the cytoskeleton, whereas decreases are seen in digestive enzymes and proteins related to metabolism. Many protein changes however, are not consistent between studies and only the most recent studies are rigorous and quantitative. By contrast, biomarker studies have focused on pancreatic juice and plasma of humans with disease and often are directed at distinguishing chronic pancreatitis from cancer. Chronic pancreatitis has also been investigated in tissue sections of histological samples. In this review, the results of studies to date are described as well as coverage of the methods used and special issues that must be considered. Areas are pointed out that are worthy of future study.