Catalyst layer degradation has become an important issue in the development of proton exchange membrane (PEM) fuel cells. This paper reviews the most recent research on degradation and durability issues in the catalyst layers including: (1) platinum catalysts, (2) carbon supports, and (3) Nafion ionomer and interfacial degradation. The review aims to provide a clear understanding of the link between microstructural/macrostructural changes of the catalyst layer and performance degradation of the PEM fuel cell fueled with hydrogen under normal operating or accelerated stress conditions. In each section, different degradation mechanisms and their corresponding representative mitigation strategies are presented. Also, general experimental methods are classified and various investigation techniques for evaluating catalyst degradation are discussed.