This article reviews the development, current theories behind the mechanism of action and clinical use of subatmospheric pressure wound therapy with the vacuum-assisted closure device. An evolving list of indications for subatmospheric pressure therapy is discussed including its use in chronic wounds, traumatic wounds and orthopedic salvage, infected sternal wounds, management of the open abdomen, enterocutaneous fistulae, burn wounds, skin grafts and dermal substitutes, as well as systemic disease processes, such as myoglobinuria. The vacuum-assisted closure device Instill system is also reviewed, in which subatmospheric pressure therapy has been combined with the instillation of therapeutic solutions for the treatment of difficult infected wounds.