Abstract: Refractory high-entropy alloys (RHEAs) are being developed to meet mechanical, thermal and chemical requirements that exceed what current super-alloys can withstand. This review explains how composition design, processing routes and the resulting microstructures now combine to realize that potential. We first link phase selection in BCC-, FCC- and dual-phase RHEAs to atomic-size mismatch, mixing enthalpy and valence-electron concentration, and compare manufacturing paths ranging from arc melting to powder metallurgy, additive manufacturing and vapor deposition, showing how each reshapes grain structure and defect chemistry to improve high-temperature strength, corrosion resistance and irradiation tolerance. Computation-led tools—density-functional theory, calculation of phase diagrams and machine learning—shrink the enormous composition space and predict phase stability, transformation paths and oxidation behavior with increasing accuracy. At the same time, metastable TRIP/TWIP alloys, coherent superlattices and nanoscale heterostructures demonstrate that chemical complexity can overcome the traditional trade-off between strength, ductility and damage tolerance. We propose that combining multiscale simulation, in situ characterization and closed-loop data analysis will speed up the transition of RHEAs from laboratory studies to working engineering components.