Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases. The MMPs belong to a larger family of proteases known as the metzincin superfamily. MMPs are capable of degrading all kinds of extracellular matrix proteins, but also can process a number of bioactive molecules. The activity of MMPs is thought to be balanced by endogenous factors released by tumors and stromal components. Thus, MMPs play a major role on invasion, metastasis, and angiogenesis. Among them, MMP-2 and MMP-9 are important in metastasis, while MMP-1 is important in rheumatoid arthritis and osteoarthritis. In recent years, inhibiting the degradation process of MMPS can serve as a potential strategy for cancer therapy. Tanomastat (also known as BAY 12-9566) is an orally active, non-peptidic biphenyl matrix metalloproteinases (MMPs) inhibitor. This compound has a Zn-binding carboxyl group, and is effective on MMP-2, MMP-3, MMP-9 and MMP-13. Especially, Tanomastat inhibits angiogenesis, tumor regrowth, and the growth of lung metastases. For example, in vitro, Tanomastat prevents matrix invasion by endothelial cells in a dose-dependent manner, without affecting cell proliferation. In addition, Tanomastat inhibits tubule formation by human endothelial cells in an in vitro model, but does not prevent the proliferation of endothelial and human breast cancer cells. Besides, in vivo, Tanomastat (oral administration, daily) inhibits basic fibroblast growth factor-induced angiogenesis. Moreover, in the MDA-MB-435 human mammary carcinoma xenograft model, Tanomastat inhibits local tumor regrowth by 58% without causing any toxic effect. Meanwhile, it inhibits the number and volume of lung metastases by 57 and 88%, respectively. To sum up, Tanomastat is an orally active, non-peptidic biphenyl MMPs inhibitor, with antiangiogenic, anti-invasive and antimetastatic activities.