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This article summarizes the results of a comprehensive review of the literature on the use of negative pressure wound therapy with reticulated open cell foam (NPWT/ROCF) as delivered by V.A.C.® Therapy (KCI, San Antonio, TX) in pediatric patients. A review of the literature revealed 20 articles that discussed the use of NPWT/ROCF in exclusively pediatric patients. Nine articles were retrospective reviews, and 11 were case studies. This review discusses the insights from these articles. This review discusses the versatility of NPWT/ROCF for use with pediatric patients with infected wounds; full-thickness burns; open fractures; large soft tissue wounds; surgical wounds of the chest, abdomen, and spine; pilonidal disease; and pressure ulcers. NPWT/ROCF has been used in children as young as a few weeks of age, and in children with comorbidities such as congenital heart disease, immunosuppression, and spina bifida. Wound healing in children can be delayed by impaired perfusion, infection, edema, and poor nutrition. Clinical considerations for using NPWT/ROCF in children can include differences in healing due to higher granulation rates requiring more frequent dressing changes, poor nutritional status, small size, and low weight. With pediatric patients, there is no consensus on foam (white or black) selection, optimum amount of negative pressure, frequency of NPWT/ROCF dressing changes, and interposing contact layer selection. Randomized prospective studies are needed to make recommendations for safe and efficacious clinical practice. Research regarding the effects of dressing types, adjunctive treatment, and wound healing in neonates and children is needed.