As a candidate cathode material for next-generation Li-ion batteries or solid state batteries, the spinel LiNi0.5Mn1.5O4 is appealing researchers' interest. The 5 V spinel material of LiNi0.5Mn1.5O4 had ordered and disordered phases, and crystal structure, synthetic method and electrochemical reaction mechanism of which were discussed. Also, its electronic conductivity and lithium ion diffusion coefficient were highlighted compared with other cathode materials. The advantages of LiNi0.5Mn1.5O4, such as high discharge plateau, good rate performance, high thermal stability, abundant manganese resources and low cost, were introduced. Then technical obstacles hindering the industrialization of LiNi0.5Mn1.5O4 were discussed, including poor cycle performance at high temperature, low cycling coulombic efficiency, metal dissolution and phase transition, electrolyte decomposition at high voltages, gas generation in full cells. The main reason negatively affected the electrochemical performance of Li-ion batteries was electrochemical oxidation of carbonate esters at the LiNi0.5Mn1.5O4/electrolyte interface which resulted in Ni/Mn dissolution, crystal structural transformation and surface film formation, and eventually led to lower electronic conductivity and Li+ transport kinetics in Li-ion batteries. Some solution ideas were summarized at the material level, such as microscopic morphology control, new binder slurry strategy, doping, coating, high voltage matching electrolytes, synthetic control, and these material solution ideas should be coordinated with full cell design. In addition, this review speculated a few possible application scenarios on basis of its merits, for instance, start-and-stop power supply, low-temperature application, power tools and so on. Commercialization of LiNi0.5Mn1.5O4 relies on elaborate construction design at the battery level beside the materials design. More wide and thorough application research needs to be done to push the industrialization of LiNi0.5Mn1.5O4.