Advanced, high temperature materials used in aircraft and gas turbine engine components require accurate diagnostic methods to measure existing damage and determine remaining life with low uncertainties at any point in component life. A complicating factor is that under operational conditions, a number of different damage mechanisms occur simultaneously within the exposed material making microstructural assessment exceedingly complex. Photon Induced Positron Annihilation (PIPA) and related technologies have demonstrated the capability to quantify operational damage accumulation in single crystal, nickel based turbine engine components and correlate this measurement data with known operational histories. PIPA provides quantifiable measurement of damage accumulation at any stage of component life, leading to remaining life predictions with a high degree of accuracy and providing suitable statistical data on the likelihood of failure. Results of PIPA studies performed to assess the relative effects of temperature, fatigue, and thermomechanical damage on nickel based superalloy components will be discussed.