Abstract: Fibronectin extra-domain B (ED-B) has been a good target in new drug development, several relevant antibody drugs are in phase Ⅱ or Ⅲ clinical trials for metastatic melanoma, soft-tissue sarcoma and so on. Some data of phase Ⅱ clinical trials shows that ED-B antibody drugs (L19-IL2 and L19-TNF α) for melanoma are significantly superior to PD-1 antibody drugs. This article describes several aspects of ED-B, such as biological characteristics, the development of targeted drugs, and the potential therapeutic applications, including modifying protein drug structure, constructing fusion protein, expanding indications, developing companion diagnostics and individual treatments. We also discuss how to promote original innovation in drug discovery, which might help to find new development focus.