Severe sepsis and septic shock continue to plague intensive care units, leading to significant morbidity and mortality (Vincent et al., 2007). During the pathogenesis of sepsis, patients often develop multiple organ failure (MOF), which is believed to be the main cause of death (Vincent et al., 2007), indicating that either treatment or prevention of MOF could have profound therapeutic implications. However, despite extensive research in this field, the mechanisms and cellular pathophysiology involved in the transition of sepsis to MOF remain unclear, likely due to their immense complexity and cross-talk between signalling pathways. This chapter aims to highlight the current knowledge regarding the pathophysiology of sepsis-induced organ dysfunction and failure, specifically outlining the current state of knowledge regarding septic-induced dysfunction of the lung, liver, kidney, cardiovascular system and brain For each of these organ systems, we will identify the major cell types prone to damage and briefly describe the key molecular pathways thought to contribute to this phenomenon, thereby ascertaining possible novel therapeutic targets.