Reduced activation ferritic-martensitic (RAFM) and oxide dispersion strengthened (ODS) steels are the most promising candidates for fusion first-wall/blanket (FW/B) structures. Performance of these steels will deteriorate in-service due to neutron damage and transmutation-induced gases like helium/hydrogen at elevated operating temperatures. Here, after highlighting the operating conditions of fusion reactor concepts and a brief overview, the major irradiation-induced degradation challenges associated with RAFM/ODS steels are discussed. Their long-term degradation scenarios such as (i) low temperature hardening-embrittlement (LTHE) - including dose-temperature dependent yield stress, tensile elongations, necking ductility, test temperature effect on hardening, Charpy impact ductile to brittle transition temperature and fracture toughness, (ii) inter-mediate temperature cavity swelling, (iii) the effect of helium on LTHE and cavity swelling, (iv) irradiation creep and (v) tritium management issues are reviewed. The potential causes of LTHE are discussed that highlights need for advanced characterization techniques. Mechanical properties including tensile/Charpy impact of RAFM and ODS steels are compared to show that current generation of ODS steels also suffer from LTHE, and they can show irradiation hardening up to high temperatures, ~400-500 °C. To minimize this, future ODS steel development for FW/B specific application should target materials with lower Cr concentration (to minimize α’) and minimize other elements that could form embrittling phases under irradiation. RAFM steel designing activities targeting improvements in creep and LTHE are reviewed. The need to better understand synergistic effects of helium on thermo-mechanical properties in the entire temperature range of FW/B is highlighted. Because fusion operating conditions will be complex including stresses due to magnetic field, primary loads like coolant pressure, secondary loads from thermal gradients, and due to spatial variation in damage levels and gas production rates, an experimentally validated multi-scale modelling approach is suggested as a pathway to future reactor component designing such as for the fusion neutron science facility