The pharmacogenetic approach to anti-angiogenic therapy should be considered a possible strategy for many pathological conditions with high incidence in Western countries, including solid tumors, age-related macular degeneration or endometriosis. While pharmacogenetic studies are building stronger foundations for the systematic investigations of phenotype-genotype relationships in many research and clinical fields of medicine, pharmacogenetic data regarding anti-angiogenic drugs are still lacking. Here we review preclinical and clinical genetic studies on angiogenic determinants such as vascular endothelial growth factor and vascular endothelial growth factor receptor-2. We suggest that pharmacogenetic profiling of patients who are candidates for the currently available anti-angiogenic agents targeting vascular endothelial growth factor and vascular endothelial growth factor receptor-2 may aid the selection of patients on the basis of their likelihood of responding to the drugs or suffering from toxicity.