In this chapter, we show how the thermodynamic relations developed in the preceding chapters can be applied to determine the onset of fatigue failure. Specifically, we focus our attention to evaluating entropy generation and determining the fatigue life of the metals. Several illustrative examples are presented that bring to light the advantages of using the principles of thermodynamics over conventional approaches. For example, the prediction of fatigue life under variable amplitudes has always been complicated and no universally accepted treatment is available. To this end, the role of thermodynamic entropy offers a path forward.