The Physics-of-Failure (PoF) is a science-based approach to reliability that uses modeling and simulation to design-in reliability. This approach models the root causes of failures such as fatigue, fracture, wear, and corrosion. Computer-Aided Design (CAD) tools have been developed to address various loads, stresses, failure mechanisms and sites. PoF uses knowledge of basic failure processes to prevent failures through robust design and manufacturing practices, and aims to: Design-in reliability up front; Eliminate failures prior to testing; Increase fielded reliability; Promote rapid, cost effective deployment of Health and Usage Monitoring Systems (HUMS); Improve diagnostic and prognostic techniques and processes; and, Decrease operational and support costs. This guide provides a high level overview of the methodology, process and advantages to performing a PoF assessment.