Advanced alloys with both high strength and ductility are highly desirable for a wide range of engineering applications. Conventional alloy design strategies based on the single-principle element are approaching their limits in further optimization of their performances. Precipitation-hardened high-entropy alloys (HEAs), especially those strengthened by coherent L12-nanoparticles, have received considerable interest in recent years, enabling a new space for the development of advanced structural materials with superior mechanical properties. In this review, we highlight recent important advances of the newly developed L12-strengthened HEAs, including the aspects of computation-aided alloy design, unique properties, atomic-level characterization, phase evolution, and stability. In particular, we focus our attention on elucidating fundamental scientific issues involving the alloying effects, precipitation behaviors, mechanical performances, and the corresponding deformation mechanisms, all of which provide a comprehensive metallurgical understanding and guidance for the design of this new class of HEAs. Finally, future research directions and prospects are also critically assessed.