The process of new blood vessel growth, angiogenesis, involves orchestrated alterations in endothelial cell interactions with adjacent cells and with components of the underlying basement membrane matrix. The activity of matrix metalloproteinases (MMPs), proteases that can cleave basement membrane and interstitial matrix molecules, has been shown to be necessary for angiogenesis as it occurs in several different in vivo and in vitro models. This review discusses the potential roles of two particular MMPs, MMP-2 and MT1-MMP, in angiogenesis, with emphasis on current understanding of how endothelial cell-extracellular matrix interactions may regulate the production of these MMPs via matrix-induced signaling leading to transcriptional activation and subsequent formation of active multiprotease complexes on the cell surface.