Vascular endothelial growth factor receptor-1 (VEGFR-1) is a member of the VEGFR family, and binds VEGF-A, PlGF, and VEGF-B. An important feature of VEGFR-1 is that, unlike other VEGFR genes, it expresses two types of mRNA, one for a full-length receptor and another for a soluble short protein known as soluble VEGFR-1 (sFlt-1). The binding-affinity of VEGFR-1 for VEGF-A is one order of magnitude higher than that of VEGFR-2, whereas the kinase activity of VEGFR-1 is about 10-fold weaker than that of VEGFR-2. Through its ligand-binding region and by trapping ligands, VEGFR-1 plays a negative role in angiogenesis at embryogenesis. In adulthood, however, VEGFR-1 is expressed not only on endothelial cells but also on macrophages, and promotes the function of macrophages, inflammatory diseases, cancer metastasis, and atherosclerosis via its kinase activity. Soluble VEGFR-1 is abnormally overexpressed in the placenta of preeclamptic patients, and suggested to cause the major pathological symptoms on the maternal side such as hypertension and renal dysfunction, most likely by blocking the physiological VEGF-A. VEGFR-1 including its soluble form is involved in a variety of human illnesses, making it an important target in the development of new strategies to suppress disease.