In modern gas-turbine engines, high temperatures and pressures, in addition to excessively lofty rotational speeds, are essential requisites as they play a determining role in engine efficiencies. However, high temperatures are known to significantly affect material mechanical properties, and tend to promote oxidation. An ideal material for this application, therefore, is not only expected to be fatigue-/creep-resistant but also to exhibit high mechanical-property stability against temperature changes and oxidation. This is because, typical operating conditions constitute mainly of excessively high thermal stresses, tempestuous mechanical stresses in prohibitively corrosive exhaust gases. Nickel-based superalloys, one of the materials widely employed for this purpose, are a unique class of materials, designed for the manufacture of components that form a backbone of gas turbine-engines. In addition to the significant influence microstructural features have on their mechanical behaviour, the synergetic influences between the characteristics of the operating conditions tend to be enormous. This paper presents an overview of the role microstructure plays on the mechanical behaviour of nickel-based superalloys. Differences in the chemical composition, in addition to the roles played by various elements, are discussed, including relevant, essential and important characteristics of the resulting nano- and micro-scale features. Mechanical behaviour under fatigue, creep and creep-fatigue loading conditions is investigated, particularly, how microstructure, temperature and loading regimes, affect fatigue, creep and creep-fatigue behaviour.