Angiogenesis is a multi-step process leading to the formation of new blood vessels from pre-existing vasculature and it is necessary for primary tumor growth, invasiveness and development of metastasis. Experimental and clinical data demonstrated that breast cancer is an angiogenesis-dependent disease and that the vascular endothelial growth factor (VEGF) family plays a key role it being a highly expressed and selective endothelial cell growth factor. Preclinical studies have shown that the angiogenic switch occurs early in the multistage process of breast cancer development. Targeting the molecular pathways involved in tumor progression by biologically-designed treatments is a new therapeutic paradigm aimed to reach cancer growth control. A number of possible therapeutic targets for antiangiogenic agents have been identified. Here we discuss the therapeutic approach based on inhibition of angiogenesis in the context of breast cancer with a focus on the early clinical studies on antiangiogenic agents in advanced disease.