Extrasynaptic NMDA receptors, which locate in the extrasynaptic site rather than synaptic site have shown to mediate cell death pathway, while synaptic NMDA receptors play an important role in learning and memory and mediate cell survival pathway. This review discussed the reasons of their different distribution between synaptic and extrasynaptic sites, the different molecular mechanisms for signaling pathways of cell fate, as well as their roles in Alzheimer's disease (AD) based on the structure and function of NMDA receptors. Finally, we proposed a reasonable outlook on the treatment of AD from the view of extrasynaptic NMDA receptor.