Blocking the interaction between vascular endothelial growth factor (VEGF) and its receptors has proven successful in the treatment of cancer and macular degeneration. Monoclonal antibodies such as bevacizumab (Avastin, Genentech) prohibit the binding of VEGF to its receptor and the resulting recruitment of blood vessels to tumor sites. Alternatively, peptides that bind VEGF may provide similar treatment or act as a targeting moiety for drug delivery or tumor detecting systems. Like their antibody or aptamer counterparts, peptide ligands must bind with high affinity to VEGF and not other circulating proteins. To achieve these properties, a combinatorial library was screened for peptides binding to VEGF with high affinity and which retained binding in the presence of competing proteins (serum). Directed evolution followed by the introduction of multivalent binding interactions resulted in high affinity, specific peptide ligands for VEGF. These complex ligands consist of two binding motifs that, when joined, show improved binding over a single peptide motif alone.