Poststernotomy mediastinitis, also commonly called deep sternal wound infection, is one of the most feared complications in patients undergoing cardiac surgery. The overall incidence of poststernotomy mediastinitis is relatively low, between 1% and 3%, however, this complication is associated with a significant mortality, usually reported to vary between 10% and 25%. At the present time, there is no general consensus regarding the appropriate surgical approach to mediastinitis following open-heart surgery and a wide range of wound-healing strategies have been established for the treatment of poststernotomy mediastinitis during the era of modern cardiac surgery. Conventional forms of treatment usually involve surgical revision with open dressings or closed irrigation, or reconstruction with vascularized soft tissue flaps such as omentum or pectoral muscle. Unfortunately, procedure-related morbidity is relatively frequent when using conventional treatments and the long-term clinical outcome has been unsatisfying. Vacuum-assisted closure is a novel treatment with an ingenious mechanism. This wound-healing technique is based on the application of local negative pressure to a wound. During the application of negative pressure to a sternal wound several advantageous features from conventional surgical treatment are combined. Recent publications have demonstrated encouraging clinical results, however, observations are still rather limited and the underlying mechanisms are largely unknown. This review provides an overview of the etiology and common risk factors for deep sternal wound infections and presents the historical development of conventional therapies. We also discuss the current experiences with VAC therapy in poststernotomy mediastinitis and summarize the current knowledge on the mechanisms by which VAC therapy promotes wound healing. Finally, we suggest a structured algorithm for using VAC therapy for treatment of poststernotomy mediastinitis in clinical practice.