Tissue inhibitors of metallproteinases (TIMPs) control metallo proteinases (MMPs), which are a large class of catalytic enzymes involved in a wide range of processes regulating tissue homeostasis. MMPs are formed as inactive zymogens which must be cleaved to become active. Activated MMPs are inhibited by four TIMPs. TIMPs form non-covalent complexes with MMPs. MMPs function through a divalent metal ion in their catalytic domain. TIMPS bind to this catalytic domain in a 1:1 ratio. TIMP and MMP expression and function are tightly regulated in order to contain a balance in proteolysis and proteolysis inhibition. Each TIMP targets multiple enzymes. TIMPs are ca 21Kda and share approximately 40% in amino acid sequence. The inhibitory capacity is located within the N-terminal domain. TIMP1 and TIMP3 are inducible, cell cycle regulated, glycosylated proteins expressed in many organs. TIMP2 is ubiquitous and constitutively expressed, whereas TIMP3 is tissue restricted. As extracellular proteins, the secretion, endocytosis and binding partners of TIMPs influence their localization. All TIMPs are secreted, but only TIMP3 is incorporated into the matrix. TIMP2 is associated with cancers, sclerosis and kidney injury. TIMP2 has a unique function given its crucial role in the formation of the MT1-MMP–TIMP2–proMMP2 ternary complex responsible for proMMP2 activation at the cell surface.