Research on the chemistry of high-energy-density transition metal oxide cathodes (TMOCs) is at the forefront in the pursuit of lithium-ion batteries with increased energy density. As a critical component of these cathodes, binders not only glue cathode active material particles and conducting carbons together and to current collectors but also play pivotal roles in building multiscale compatible interphases between electrolytes and cathodes. In this review, we outline several vital design considerations of high-voltage binders, several of which are already present in traditional binder design that need to be highlighted, and systematically reveal the chemistry and mechanisms underpinning such binders for in-depth understanding. Further optimization of the design of polymer binders to improve battery performance is also discussed. Finally, perspectives regarding the future rational design and promising research opportunities of state-of-the-art binders for high-voltage TMOCs are presented.