Sepsis brings about neuroendocrine dysfunction in children that differs significantly from that of adults and can thus be difficult to interpret and manage. Aggressive treatment of sepsis with appropriate and judicious use of antibiotics remains a top priority. Strict glycemic control in children has been associated with significant risk of hypoglycemia, which may independently contribute to morbidity and mortality. Timely initiation of hydrocortisone in persistently hypotensive children with fluid-refractory, catecholamine-resistant shock is controversial, but its use in children with suspected or proven adrenal insufficiency is suggested. Fluid and electrolyte abnormalities must be corrected. Treatment of thyroid dysfunction has been shown to be beneficial in certain specific populations but cannot be extrapolated to all septic patients with the current available data.