The aircraft engine industry is constantly striving to increase the operating temperature and stresses in hot section engine components, a goal that can only be achieved by accurately modeling and predicting damage mechanisms of potential engine materials. The objective of this work is to develop physically-based models that are able to accurately predict the high temperature crack initiation behavior of Rene 88DT, a commonly used aircraft engine disk material, under low cycle fatigue (LCF) conditions. Two different microstructural conditions were produced by subjecting the material to two separate heat treatments; the heat treatments were selected so that grain size remains the same but the size distribution of the strengthening gamma prime precipitate is different between the two conditions. LCF experiments were performed on specimens from each condition at 650C and R = -1 under strain ranges of 0.66%, 0.75%, and 1.5%. A third microstructural condition with a similar grain size but different gamma prime size distribution was tested by another source at 650C and R = 0 under strain ranges of 0.66%, 0.79%, 0.94%, and 1.14%. The results indicate that there are two competing crack initiation mechanisms: initiation from a microstructural defect such as an inclusion and initiation from slip band cracking. A physically based model, in the form of a modified Fatemie-Socie parameter, is utilized to predict the crack initiation mechanism and approximate cycles to failure based on the microstructure of the material and applied strain. Long crack growth models are also developed to model crack growth from subsurface inclusions and surface semi-elliptical cracks. These models predict that long crack growth is a small portion of the total fatigue life in these conditions, which suggests that the majority of the fatigue life is spent initiating a dominant fatigue crack.