N-methyl-D-aspartate (NMDA) receptor plays an important role in the function of the nervous system. The NR2B subunit is the regulatory subunit of NMDA receptor, which is closely related to the neuroprotection of hypoxia / ischemia. Phosphorylation of NR2B is considered to be an important mechanism to regulate the NMDA receptor function and plays an important role in ischemic / hypoxic neuroprotection through the change in phosphorylation. This review discusses the development of the NR2B subunit of NMDA receptor and the relationships between the structure, function, phosphorylation, signaling pathway and ischemic / hypoxic neuroprotection to provide a theoretical foundation to prevent and treat hypoxic / ischemic brain diseases with NR2B subunit as the target.