Classically, structural component fatigue design is based on testing and empirical models. First a series of average stress-life curves are generated from fatigue tests. Constant life diagrams are then developed accounting for mean stress effect, casting quality, surface finish, volume and other factors. Component design is then based on keeping the effective alternating stress below the diagram limit stress. While this procedure has worked well to design many components, it is based on extensive fatigue testing and empirical stress reduction factors. Thus, material and process improvements and computerization of the design process are difficult to incorporate into this test/empirical based design methodology.Fracture mechanics and damage tolerant design methodologies are used in aerospace for fatigue design. These methods predict well the fatigue life for surface scratches (rogue inspectable flaws) of about 0.25-1.27 mm in size. As crack measurement techniques have improved, researchers examining small crack growth have discovered microcracks growing from microstructural features approximately 0.013-0.25 mm in size. These microcracks grow from very early in a structure's life. The principal types of microstructural features of concern are micropores and constituent particles. These microstructural features act as possible sites for the formation of fatigue cracks.The microstructure of a metallic part shows variability from point to point in the structure. In wrought products, variability in the deformation can cause this inhomogeneity, while in cast parts variability in the solidification rate can be responsible. Process models or testing can be used to predict this variability and determine the distributions of the important microstructural features. Using a probabilistic fracture mechanics model, these critical feature distributions can be used to predict a structure's reliability. Linking process and crack growth models with standard finite element codes will enable structural design to optimize material microstructure. This paper discusses a microstructurally based fatigue model and demonstrates application to cast aluminum alloys. A discussion on the use of microstructural models in structural design is highlighted.