Sepsis represents a complex clinical syndrome of significant morbidity and mortality. This continues to be the case in intensive care units around the world, despite extensive use of antibiotics, aggressive surgical intervention and optimization of nutritional support. Furthermore, the failure of > 30 anti-inflammatory mediator therapeutic trials implies, beyond the issue of trial design, there remains the necessity to develop a better understanding of the evolving pathophysiology of this syndrome. Studies indicate that the development of marked immune suppression in sepsis is more often associated with morbid outcome. Dendritic cells, a critical immune cell type bridging the innate and adaptive immune response, not only are affected (killed) by the systemic inflammatory response but also contribute to (by impaired function) the development of immune suppression during sepsis. Here the authors attempt to review emerging data indicating the key role dendritic cells may play in sepsis-induced immune suppression. Undoubtedly, a better understanding of the dendritic cell's response during sepsis will be critical to developing novel strategies for fighting this deadly disease.