AbstractConventional alloys are usually based on a single host metal. Recent high-entropy alloys (HEAs), in contrast, employ multiple principal elements. The strength of HEAs is considerably higher than traditional solid solutions, as the many constituents lead to a rugged energy landscape that increases the resistance to dislocation motion, which can also be retarded by other heterogeneities. The wide variety of nanostructured heterogeneities in HEAs, including those generated on the fly during tensile straining, also offer elevated strain-hardening capability that promotes uniform tensile ductility. Citing recent examples, this review explores the multiple levels of heterogeneities in multi-principal-element alloys that contribute to lattice friction and back stress hardening, as a general strategy towards strength–ductility synergy beyond current benchmark ranges.