INTRODUCTION: Ramucirumab (IMC-1121B) is a fully humanized IgG1 monoclonal antibody, targeting the extracellular domain of VEGF receptor 2 (VEGFR2). Numerous Phase I - II trials in various malignancies have shown promising clinical antitumor efficacy and tolerability. Most recently, the large Phase III REGARD trial evaluated ramucirumab in patients with refractory metastatic gastric cancer. Patients receiving ramucirumab experienced a median overall survival of 5.2 months compared to 3.8 months on placebo. AREAS COVERED: The purpose of this article is to review the preclinical motivation for VEGFR2-targeted therapies and survey recent data from clinical trials involving ramucirumab, as well as highlight ongoing studies. EXPERT OPINION: Rational multi-target approaches to angiogenesis are needed to overcome resistance mechanisms. Predictive angiogenic biomarkers are also needed to optimize patient selection for novel anti-angiogenic agents.