Angiogenesis, the creation of neovasculature from native blood vessels, is a prerequisite for many physiological and pathological processes. Recently, C-terminal tail fragments of several basement-membrane proteins such as endostatin, tumstatin and endorepellin have been shown to inhibit angiogenesis. Although there seems to be little or no homology among them, a common theme is that these fragments modulate endothelial cells by distinct interactions with integrins and activate distinct intracellular signaling cascades that often lead to disruption of the actin cytoskeleton. In this article, we focus on recent advances regarding the mechanism of action of these angiostatic fragments and the emerging concept of similarities among them, with the underlying premise that appreciating these similarities might lead to improved therapeutics.