Microstructural influences on notch fatigue initiation, short and long crack propagation in a number of Ni-base superalloy systems are compared. The key role of defects either preexisting (such as porosity) or evolving during service (e.g. defects produced by carbide oxidation) is highlighted, and the importance of initiating defect location and grain size on subsequent crack propagation modes identified. Increased grain size is a key microstructural feature in improving fatigue resistance, in U720Li materials, but single crystal specimens are not found to offer significant fatigue resistance improvements, due to the differing alloy chemistry (oxidation resistance), crack propagation modes and importance of considering secondary orientation in crack path determination.