Angiogenic blood vessel growth is essential to ensure organs receive adequate blood supply to support normal organ function and homeostasis. Angiogenesis involves a complex series of cellular events through which new vessels grow out from existing vasculature. Growth factor signaling, layered over a range of other signaling inputs, orchestrates this process. The response of endothelial cells (ECs) to growth factor signals must be carefully controlled through feedback mechanisms to prevent excessive vessel growth, remodeling or destabilization. In this article, we summarize recent findings describing how ECs respond to growth factor signals during blood vessel development and homeostasis and how perturbation of these responses can lead to disease.