Future advanced nuclear plants are considered to operate as cogeneration plants for electricity and heat. Metals and alloys will be the main portion of structural materials employed (including fuel claddings). Due to the operating conditions these materials are exposed to damaging conditions like creep, fatigue, irradiation and its combinations. The paper uses the most important alloys: ferritic-martensitic steels, superalloys, oxide dispersion strengthened steels and to some extent titanium aluminides to discuss its responses to these exposure conditions. Extrapolation of stress rupture data, creep strain, swelling, irradiation creep and creep-fatigue interactions are considered. Although the stress rupture- and the creep behavior seem to meet expectations, the long design lives of 60 years are really challenging for extrapolations and particularly questions like negligible creep or occurrence of diffusion creep need special attention. Ferritic matrices (including oxide dispersion strengthened (ODS), steels) have better irradiation swelling behavior than austenites. Presence and size of dispersoids having a strong influence on high-temperature strength bring only insignificant improvements in irradiation creep. A strain-range-separation based approach for creep-fatigue interactions is presented which allows a real prediction of creep-fatigue lives. An assessment of capabilities and limitations of advanced materials modeling tools with respect to damage development is given.