Polymer electrolyte membranes (PEM) are semipermeable barriers sandwiched between two catalyzed electrodes in a polymer electrolyte membrane fuel cell (PEMFC) [1,2]. The membranes serve a number of roles within the fuel cell: proton conductor, electronic insulator, and gas separator. Perfluorosulfonic acid (PFSA) is the most widely used polymeric electrolyte membrane material in PEMs at this time [3]. In order to maintain the performance and life of fuel cells, the proton conductivity of the PEM should be close to 0.1 S cm-1. At the same time, the properties of the membrane must be able to accommodate pure hydrogen and reformate hydrogen, which are the most commonly used fuels. Thus, the hydrogen permeability through this membrane should be less than 10-12 mol H2 cm-1 s-1 kPa-1 to avoid gas crossover. Operating parameters, such as temperature, pressure, and relative humidity, have important effects on these properties and on determining the lifetime of fuel cells. Every engineering and scientific device has limitations associated with its operation, particularly over the long term, due to the effects of degradation and contamination. The PEM fuel cell is no exception in this regard. This chapter begins with an overview of membrane chemistry and different membrane degradation mechanisms in section 5.1. It follows in section 5.2 with a discussion of the various contamination sources and associated degradation mechanisms. Finally, the chapter closes with a discussion of strategies to mitigate PEM contamination. © 2010 by Taylor and Francis Group, LLC.