Sepsis is a significant public health problem that affects children and adults alike. Despite some similarities in the approach to pediatric and adult septic shock, there are key differences as it relates to pathophysiology, clinical presentation, and therapeutic approaches. In this review article, we discuss these differences under 4 headings: a) Developmental differences in the hemodynamic response, b) Activated Protein C, c) Thrombocytopenia associated multiple organ failure and d) Hemophagocytic Lymphohistiocytosis (HLH).