ABSTRACT: Cathepsins are a class of globular lysosomal proteases that are known to be responsible for protein degradation. They have many biological roles besides proteolysis, such as apoptosis wound healing angiogenesis, proenzymatic activation, bone remodeling, and resorption. The role of cathepsins in pathogenesizing systemic diseases such as cancer, bronchial asthma, atherosclerosis, neurological disorders, rheumatoid arthritis and osteoarthritis has been involved. This review emphasizes the role of cathepsins in multiple oral diseases such as periodontitis, odontogenic cysts, ameloblastoma, tumors of the salivary glands and malignant melanoma.