To increase efficiency, a wide range of energy-related applications are pushing components to higher temperatures where environmental degradation can be life limiting. Unlike mechanical properties such as creep, there is no simple degradation parameter to capture, for example, the time-temperature-thickness limitations of candidate alloys. Also, the degradation mechanism varies greatly depending on the environment. For complex environments such as molten salts and liquid metals, the first assessment step is determining the degradation mechanism. For simpler high temperature gas reactions, the mechanisms are better understood and the issue becomes quantifying the degradation rate in a manner useful to component designers. Modeling is rapidly evolving and more sophisticated computational methods are now being adopted. Case studies will be presented from various projects to illustrate the stages of compatibility assessments from identifying mechanisms to predicting lifetimes. Research sponsored by the US DOE, Offices of Fossil Energy and EERE.