The use of negative pressure wound therapy (NPWT) continues to be an important tool for surgeons. As the use and general acceptance of NPWT have grown, so have the indications for its use. These indications have expanded to include soft tissue defects in trauma, infection, surgical wound management, and soft tissue grafting procedures. Many adjuvants have been engineered into newer generations of NPWT devices such as wound instillation of fluid or antibiotics allowing surgeons to further optimize the wound healing environment or aid in the eradication of infection. This review discusses the recent relevant literature on the proposed mechanisms of action, available adjuvants, and the required components needed to safely apply NPWT. The supporting evidence for the use of NPWT in traumatic extremity injuries, infection control, and wound care is also reviewed. Although NPWT has a low rate of complication, the surgeon should be aware of the potential risks associated with its use. Furthermore, the expanding indications for the use of NPWT are explored, and areas for future innovation and research are discussed.