High-entropy alloys (HEAs), which are defined as near-equimolar alloys of five or more elements, are attracting ever increasing attention because of the unique properties in a variety of applications. Recently, HEAs have already exhibited remarkable catalytic performance toward several thermal-driven and electrocatalytic reactions. HEAs not only regulate the electronic and geometric structures to a large degree but also serve as a platform to construct catalysts with unexpected performance. Herein, recent advances regarding HEA-based catalysis are systematically summarized, with a special focus on the synthetic methods for HEA-based catalysts, catalytic performance, and mechanistic understanding. Moreover, the challenges and future opportunities for this research area are carefully discussed. A series of open questions and promising directions to be explored are proposed, including synthetic methods, regulation of electronic properties, identification of active centers, and applications into photocatalysis. This Review provides an overview about the progress, challenges, and opportunities for HEA-based catalysis.