Polymer electrolyte membrane fuel cells (PEMFC) have received much attention due to their high power density, good start-stop capabilities and high gravimetric and volumetric power density compared with other fuel cells. However, certain technological challenges persist, which include the fact that conventional anode electrocatalysts are poisoned by low levels (few ppm) of carbon monoxide (CO). This review considers the mechanism of CO poisoning and the effects that it has on the PEMFC performance. The key parameters affecting CO poisoning are identified and methods used to mitigate the effects are discussed. These mitigation strategies are divided into three groups according to the means by which the technologies are applied: pre-treatment of reformate, on board removal of CO and in operando mitigation strategies.