Sepsis, septic shock, systemic inflammatory response syndrome, and Multiorgan dysfunction syndrome (MODS) remain clinical challenges in pediatric critical care. Understanding of the immune response has increased greatly over the past decade, which has certainly increased the understanding of the pathophysiology and treatment of these conditions. The future promises more exciting discoveries as we understand cellular physiology, immunity, and host responses even better. This article reviews the current knowledge about sepsis and MODS in pediatric patients and discusses the best treatment modalities while highlighting the critical aspects of nursing care for this vulnerable population.