Sepsis is a significant health problem in both critically ill children and adults. While the mortality rate from sepsis is much lower in children, sepsis is directly responsible for over 4,000 childhood deaths per year in the United States alone. At face value, this number suggests that more children die per year in the United States from sepsis as the primary cause than from cancer. Unfortunately, there are few studies on the epidemiology, pathophysiology, and management of sepsis in children. Moreover, extrapolation of adult data to critically ill children is probably not appropriate due to several key developmental differences in the host response to infection and response to therapy. Therefore, additional studies targeting sepsis in the pediatric population are urgently required.