The purpose of this review is to provide an overview of redox mechanisms, sources and antioxidants that control signaling events in ECs. In particular, we describe which molecules are involved in redox signaling and how they influence the relationship between ECs and other vascular component with regard to angiogenesis. Recent and new tools to investigate physiological ROS signaling will be also discussed. Such findings are providing an overview of the ROS biology relevant for endothelial cells in the context of normal and pathological angiogenic conditions.