MMP-8, also termed neutrophil collagenase, is a member of the matrix metalloproteinase family proteins (MMPs). Members of this family are structurally related, zinc-containing enzymes that degrade the extracellular matrix (ECM) and connective tissue proteins. MMP-8 consists of a prodomain that is cleaved upon activation, a catalytic domain containing the zinc binding site, a hinge region, and a carboxyl terminal domain with hemopexin-like repeats. Substrates of MMP-8 include type I, II, and III triple-helical collagens, gelatin peptides, proteoglycans, fibronectin, aggrecan, substance P, serpins, β-casein, and angiotensin. MMP-8 is released by neutrophils upon IL-1β IL-8, GM-CSF and TNF-α stimulation. Besides playing a role in phagocytosis, MMP-8 has been implicated in rheumatoid arthritis (RA) because of its high efficiency in infiltrating connective tissue and breaking down ECM. In fact, serum level of MMP-8 is a strong predictor of mortality in RA, as this is consistent with increased activation of neutrophils in RA. In addition, MMP-8 has been shown to play a crucial role in cardiovascular diseases by promoting atherosclerotic lesion formation. This is supported by the finding that MMP-8 knockout mice have less endothelial cells or plaque angiogenesis in the atherosclerotic plaques. In a clinical study, it was shown that the ratio of MMP-9/TIMP-1, as well as MMP-8 serum levels, could be a useful predictor of prognosis in patients with hepatocellular carcinomas.