Angiogenesis, the formation of new blood vessels is essential for diverse physiological processes such as development, but also for pathological conditions like tumor growth. Most studied in this context are tyrosine kinase signaling pathways such as those involving vascular endothelial growth factor (VEGF). There is however accumulating evidence that more pathways are as essential for angiogenesis. Knockout studies of factors in transforming growth factor β (TGF-β) signaling have for example showed that also this pathway is indispensable for angiogenesis. This review highlights our understanding of TGF-β signaling in vascular development and angiogenesis. In particular, we focus on recent insights into the role of the TGF-β type I receptor ALK1 and co-receptor endoglin in tumor angiogenesis, which provide opportunities for the development of new anti-angiogenesis therapies for treatment of cancer patients.