The intravenous administration of fluids and medications is critical for the treatment of seriously ill patients. Unfortunately, especially in infants and children, fluid infiltration into the surrounding tissue can occur. Early recognition and prompt treatment usually limits the extent of tissue damage. Early treatment may include the injection or application of medication (eg, hyaluronidase, phentolamine, or nitroglycerin ointment) and appropriate dressings. Research to guide the care of more extensive extravasation injury remains limited. At the author's institution, the protocol of care for children and infants with extensive tissue damage and necrotic tissue consists of careful debridement followed by the use of oxidized regenerative cellulose (ORC)/collagen dressings and skin replacement if needed. Research to help clinicians develop evidence-based protocols of care for both minor and more severe intravenous fluid infiltration or extravasation injury is needed.