Thermomechanical fatigue (TMF) is the general term given to the material damage accumulation process that occurs with simultaneous changes in temperature and mechanical loading. TMF may couple cyclic inelastic deformation accumulation, temperature-assisted diffusion within the material, temperature-assisted grain-boundary evolution, and temperature-driven surface oxidation, among other things. This article discusses some of the major aspects and challenges of dealing with TMF life prediction. It describes the damage mechanisms of TMF and covers various experimental techniques to promote TMF damage mechanisms and elucidate mechanism coupling interactions. In addition, life modeling in TMF conditions and a practical application of TMF life prediction are presented.