A physically-based methodology for modelling microstructurally-sensitive fatigue crack growth has been developed and shown to capture many of the experimentally observed effects associated with microstructurally-sensitive fatigue crack growth, which currently contribute to the high levels of uncertainty in lifing models. Behaviours predicted by the model cover changes in rate and path due to interactions with local microstructural features including rate changes due to local crystal orientations, deflections and retardation at grain boundaries and crack path tortuosity within grains. The ability of the model to accurately capture these key behaviours has enabled their rationalisation within a physically-based, mechanistic framework.