Sepsis is a systemic inflammatory response caused by infection and is a major cause of mortality after serious injuries and infections. The pathogenesis of sepsis involves several factors such as genetic interaction, pathogen recognition and biological processes that control host responses. Many animal models have been described by various investigators in the study of the pathobiology of sepsis and systemic inflammatory response. In this report we review all the important experimental models that have been used in the study of sepsis, including endotoxin, bacteremia, exogenous peritonitis, and exogenous cecal ligation and perforation models. Notwithstanding the limitations, these models are extensively used by investigators to understand the disease process and to perform pre-clinical studies to test various treatment strategies. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.