Angiogenesis, the process of new blood vessel formation, is regulated on both genetic and molecular levels. Pro- and anti-angiogenic stimuli maintain the angiogenic balance, and the tipping of that balance toward pro-angiogenic activity is critical for tumor growth and survival. Endogenous inhibitors of angiogenesis, many of which are fragments from large extracellular matrix proteins, counter the effect of growth factors and keep angiogenesis in check. This chapter will discuss the molecular mechanisms of endogenous inhibitors derived from type IV collagen and review the in vitro and in vivo assays available to study their role in angiogenesis.