Negative pressure wound therapy (NPWT) has overwhelmed the wound-healing world. A systematic review puts it into perspective. The authors have developed an algorithm after careful evaluation and analysis of the scientific literature supporting the use of these devices. This article describes mechanisms of action, technical considerations, wound preparation, and clinical evidence, reviews the literature, and discusses NPWT use in specific wounds, such as diabetic foot ulcers, open abdomen, pressure ulcers, open fractures, sterna wounds, grafts, and flaps. Contraindications for and complications of NPWT are outlined, and specific recommendations given for the situations in which the authors use NPWT.