Several vascular endothelial growth factor (VEGF)-targeted agents, administered either as single agents or in combination with chemotherapy, have been shown to benefit patients with advanced-stage malignancies. VEGF-targeted therapies were initially developed with the notion that they would inhibit new blood vessel growth and thus starve tumours of necessary oxygen and nutrients. It has become increasingly apparent, however, that the therapeutic benefit associated with VEGF-targeted therapy is complex, and probably involves multiple mechanisms. A better understanding of these mechanisms will lead to future advances in the use of these agents in the clinic.