In this chapter, we apply the thermodynamics concepts developed in Chapter 2 and present a degradation-entropy generation relationship with particular interest to fatigue. Also introduced in this chapter are the concepts of thermodynamic forces and fluxes. Definitions of new concepts, and degradation forces and fluxes are given, and their affiliation with thermodynamic counterparts is discussed. We proceed to formulate degradation processes within a thermodynamic framework where entropy generation is treated as a measure of exhaustion of the system’s lifespan. In other words, the degradation or aging of the system is intimately connected to the entropy production that accumulates progressively over time and degrades the system until its final breakdown.