Sepsis is a disease of dysfunctional immune response against the pathogen causing a profound immune-mediated damage to the vital organs and death of the patient in most cases. However, when sepsis is described much attention is given to monocytes/macrophages, complement system, neutrophils, cytokine storm, and T cells. Dendritic cells (DCs) get less attention in this scenario despite comprising the major immune cell population. Therefore the present review is designed to highlight the importance of DCs in the pathogenesis of sepsis, sepsis-associated immunosuppression, and organ damage. The article starts with an introduction of sepsis as a major medical problem needing an urgent therapeutic targeting. Thereafter it provides a brief information regarding classical and plasmacytoid DCs and their role in the maintenance of immune homeostasis. The subsequent sections describe the role of DCs in the immunopathogenesis of sepsis via immunoregulation, impact of sepsis on DCs including their immunometabolic changes, and their therapeutic targeting during sepsis.