Refractory metal single crystals have been applied in key high-temperature structural components of advanced nuclear reactor power systems, due to their excellent high-temperature properties and outstanding compatibility with nuclear fuels. Although electron beam floating zone melting and plasma arc melting techniques can prepare large-size oriented refractory metals and their alloy single crystals, both have difficulty producing perfect defect-free single crystals because of the high-temperature gradient. The mechanical properties of refractory metal single crystals under different loads all exhibit strong temperature and crystal orientation dependence. Slip and twinning are the two basic deformation mechanisms of refractory metal single crystals, in which low temperatures or high strain rates are more likely to induce twinning. Recrystallization is always induced by the combined action of deformation and annealing, exhibiting a strong crystal orientation dependence. The irradiation hardening and neutron embrittlement appear after exposure to irradiation damage and degrade the material properties, attributed to vacancies, dislocation loops, precipitates, and other irradiation defects, hindering dislocation motion. This paper reviews the research progress of refractory metal single crystals from three aspects, preparation technology, deformation behavior, and irradiation damage, and highlights key directions for future research. Finally, future research directions are prospected to provide a reference for the design and development of refractory metal single crystals for nuclear applications.