Subatmospheric pressure (SAP) therapy has evolved as a mainstay in the treatment of acute and chronic wounds over the past 20 years. The significant improvement in wound healing upon application of a SAP therapy system such as the Vacuum Assisted Closure (V.A.C.; KCI, San Antonio, TX) device, historically has been related to general principles such as edema reduction, bacterial clearance, and increased perfusion to the wound bed. Recent investigations have also indicated that microdeformation and regulation of biochemical mediator expression play a role in the improved outcomes seen with SAP therapy. Future studies will pursue further the mechanisms by which SAP functions to render such impressive results in wound healing.