This chapter would be a comprehensive review of the successful application of the CALPHAD method in the research and development of high-entropy alloys (HEAs) in recent years. The structure of this chapter is obedient to the conventional framework in materials science, and several topics would be covered, including composition and structure design, heat treatment and solidification processing, and some properties and performances, such as mechanical and electrochemical corrosion behaviors and high-temperature oxidation characteristics. A conclusion and outlook of the CALPHAD method are also provided at the end of this chapter. Hope this chapter could offer a thermodynamic and kinetic perspective for facilitating the field of HEA research and inspire other researchers to contribute more valuable ideas and works.