This article presents results on the development of a microstructure-based fatigue-crack-initiation model which includes explicit crack-size and microstructure-scale parameters. The current status of microstructure-based fatigue-crack-initiation models is briefly reviewed first. Tanaka and Mura’s models for crack initiation at slipbands and inclusions are then extended to include crack size and relevant microstructural parameters in the response equations. The microstructure-based model for crack initiation at slipbands is applied to predicting the crack size at initiation, small-crack behavior, and notch fatigue in structural alloys. The calculated results are compared against the experimental data for steels and Al-, Ti-, and Ni-based alloys from the literature to assess the range of predictability and accuracy of the fatigue-crack-initiation model. The applicability of the proposed model for treating variability in fatigue-crack-initiation life due to variations in the microstructure is discussed.