Durability and reliability performance is one of the most important concerns of a recently developed Thermal Regeneration Unit for Exhaust (T.R.U.E-Clean®) for exhaust emission control. Like other ground vehicle systems, the T.R.U.E-Clean® system experiences cyclic loadings due to road vibrations leading to fatigue failure over time. Creep and oxidation cause damage at high temperature conditions which further shortens the life of the system and makes fatigue life assessment even more complex. Great efforts have been made to develop the ability to accurately and quickly assess the durability/reliability of the system in the early development stage. However, reliable and validated simplified engineering methods with rigorous mathematical and physical bases are still urgently needed to accurately manage the margin of safety and decrease the cost, whereas iterative testing is expensive and time consuming. In this paper, the state-of-the-art of the current engineering technologies and practices for durability and reliability assessments is reviewed. These technologies include, but are not limited to: the traction stress analysis method, the master S-N curve based fatigue life assessment method, multi-axial cycle counting method, time domain and frequency domain based fatigue life assessment approaches, and the tolerance limit concept based design method. The complexity caused by multiple failure modes, nonlinear behavior at high temperature, damage initiation and growth are also addressed. Finally, a synthesized analysis module for durability and reliability analysis of the T.R.U.E-Clean® system developed for commercial vehicle exhaust applications is demonstrated with several case studies.