Several anti-angiogenic agents are under evaluation in breast cancer. Currently, only bevacizumab has shown its efficacy, in combination with paclitaxel, on relapse-free survival in the metastatic setting. The combination of targeted therapies (for instance, trastuzumab plus bevacizumab, lapatinib plus pazopanib, etc.) is certainly of utmost interest. However, the anti-angiogenic agents not always bring in phase III the expected effects on patient survival, and an increased toxicity of combinations versus chemotherapy only has been observed. Outside the privileged neo-adjuvant setting, it appears difficult, for technical and ethical reasons, to obtain tissue samples before and after treatment to study predictive factors of drug response and to establish surrogate makers.