Experimental endotoxemia is now recognized as a highly useful tool to better understand inflammation-induced behavioral changes and their underlying mechanisms. Advantages of this model include the ability to assess the causal effects of inflammatory mediators in a safe and highly controlled context, to assess the homeostatic (regulatory) response to inflammatory mediators within a relatively short time frame, as well as to translate findings between animals and humans. Various groups have used this model in humans, leading to variations in experimental procedures that likely affect the studied outcomes. As the use of experimental endotoxemia develops, there is a need of a standardization of the procedure to make the best use of this model in PNI. The participants in this discussion group are all leaders in the use of the model of experimental endotoxemia in humans in PNI, and will discuss the advantages, limitations, clinical relevance, and methodological considerations of this model. This discussion is intended as a first step towards developing common and optimized procedures for the use of this model across PNI groups.