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Polyethersulfone (PES) membranes have been widely used as attractive materials especially in the field of blood purification due to their great oxidative, thermal, and chemical stability, as well as outstanding mechanical properties. However, the intrinsic hydrophobic property seriously limits its application because of the relevant side effects, like biofouling, platelet activation, and coagulation. Given the importance of PES membranes for hemodialysis, various modification methods have been developed to address this challenge; and it is necessary to review the research progress in hemocompatibility enhancement of PES membranes, which is also imperative to provide more insights for the development of future PES-based hemodialyzers and perhaps to open the door to extend their applications for the next generation of blood purification instruments, like the wearable artificial kidney. Herein, we review the concept and principles of hemocompatibility for hemodialysis membranes, different strategies developed to improve the hemocompatibility of PES membranes, and the challenges and future perspectives for improvement in hemocompatibility of PES membranes. Most emphasis has been given to the modification strategies including bulk modification, blending modification, and surface modification and their salient features are highlighted.