Pancreatic cancer is an aggressive disease with rapid invasion and metastasis. Extracellular matrix degrading enzymes play an important role in cancer cell invasion and migration. Cathepsins are a group of proteolytic enzymes, which are responsible for the matrix turnover. Among the cathepsins, more number of studies have focused upon cysteine cathepsins. The function and activities of these enzymes are interwoven and their interplay causes the activation of one another by following a proteolytic cascade. This review focuses on differential expression of cathepsins in different types of pancreatic cancer and controls, importance of cathepsins in various phenomena responsible for tumorigenesis and its spread in experimental and human studies. Thus, cathepsins and its expression in pancreatic cancer may be used as potential biomarkers and may prove to be important therapeutic targets if tested clinically.