Tissue extravasation resulting from intravenous (IV) infiltration can occur as a complication of neonatal intensive care with varying degrees of morbidity. Serious extravasation can result in pain, infection, disfigurement, prolonged hospitalization, increased hospital costs, and possible litigation. Although most infiltrates resolve spontaneously after the IV catheter is removed, IV extravasations and tissue sloughing do occur in NICU patients. Specific therapies are based on assessment of the degree of the injury. The goal in managing tissue damage after IV extravasation is to improve tissue perfusion and prevent progression of tissue necrosis. This article presents an initial approach to nursing care for peripheral IV infiltrations to guide clinicians in management of this complication. The approach is based on clinical experience, descriptive studies, and reports from expert committees.