Angiogenesis is the process of new blood vessel formation and remodeling from preexisting vessels. It is a critical mechanism for tumor growth, invasion, and metastasis. This need for vascularization is a hallmark of cancer, it entails the highly regulated coordination of several signaling pathways involved in the process of cancer progression. Decades of research efforts and clinical experiences in understanding the molecular pathways regulating angiogenesis have led to the development of many innovative and promising antiangiogenic therapeutic strategies. This chapter examines the molecular mechanisms of the antiangiogenic effects of medicinal plant extracts and their bioactive compounds, which have multiple targets. We further provide a changing paradigm in therapeutic approaches in targeting angiogenesis inside the tumor microenvironment. It is anticipated that the phytochemical intervention of tumor angiogenesis could be a novel strategy for the angioprevention of cancer.