Gelatinase B (matrix metalloproteinase-9) is a secreted multidomain enzyme that is important for the remodeling of the extracellular matrix and the migration of normal and tumor cells. It cleaves denatured collagens (gelatins) and type IV collagen, which is present in basement membranes. In the immune system, this cleavage helps lymphocytes and other leukocytes to enter and leave the blood and lymph circulations. Gelatinase B also cleaves myelin basic protein and type II gelatins, and this clipping leads to remnant epitopes that generate autoimmunity, the so-called REGA model of autoimmunity. Recently, gelatinase B has been found to process cytokines and chemokines, resulting in skewed immune functions. Therefore, gelatinase B, often considered as a pure effector molecule, acts as a switch and catalyst in both innate and specific immunity, and constitutes a prototypic example of the regulation of immune functions by proteolysis.