Introduction: Monoclonal antibodies and small molecules targeting the VEGF pathway are part of the arsenal to treat malignant tumors. Antiangiogenesis therapies has been studied in breast cancer with partial success, reflected by the approval of bevacizumab in Europe but not in United States, for metastatic breast cancer (mBC). Ramucirumab is a mAb against VEGFR-2 interfering with the normal activation of this receptor by its natural ligand VEGF.Areas covered: This article will review the preclinical data available to date for ramucirumab, as well as survey the main clinical trials of antiangiogenic agents reported in breast cancer, focusing on Phase III clinical trials. It will also review the clinical trial data for ramucirumab in mBC, including the design of the Phase II trials, and report on the preliminary results of the TRIO-012 trial. This trial did not meet its primary end point in progression-free survival and has to be considered as a negative trial.Expert opinion: Despite preliminary positive data with ramucirumab in other metastatic solid tumors reported to date, the results of TRIO-012 discourage pursuing more efforts with ramucirumab in mBC unless predictive and reproducible biomarkers can be established to select those patients who are most likely to benefit from it.