Anti-angiogenic vascular endothelial growth factor A (VEGF)₁₆₅b and pro-angiogenic VEGF₁₆₅ are generated from the same transcript, and their relative amounts are dependent on alternative splicing. The role of VEGF₁₆₅b has not been investigated in as much detail as VEGF₁₆₅, although it appears to be highly expressed in non-angiogenic tissues and, in contrast with VEGF₁₆₅, is downregulated in tumors and other pathologies associated with abnormal neovascularization such as diabetic retinopathy or Denys Drash syndrome. VEGF₁₆₅b inhibits VEGFR2 signaling by inducing differential phosphorylation, and it can be used to block angiogenesis in in vivo models of tumorigenesis and angiogenesis-related eye disease. Recent reports have identified three serine/arginine-rich proteins, SRSF1, SRSF2 and SRSF6, and studied their role in regulating terminal splice-site selection. Since the balance of VEGF isoforms is lost in cancer and angiogenesis-related conditions, control of VEGF splicing could also be used as a basis for therapy in these diseases.