Infections of the mediastinum (ie, mediastinitis) are serious, are associated with high morbidity and mortality, and may result from adjacent disease with direct extension, hematogenous spread, or direct introduction into the mediastinal space. The organs and tissues involved determine the manifestations and approach to treatment of these infections. The most common ones are those secondary to perforation of the esophagus or penetrating trauma, and those that extend from an adjacent infection. Today, the most common cause of mediastinitis is direct invasion of the mediastinum after surgical intervention. Cases of mediastinitis can be classified as either acute or chronic. Two broad categories of acute mediastinitis are acute necrotizing mediastinitis and poststernotomy mediastinitis. Chronic mediastinitis has been arbitrarily subdivided into two categories: (1) granulomatous mediastinitis, and (2) fibrosing or sclerosing mediastinitis. However, these likely represent a continuum of chronic infection. In cases of acute mediastinitis, treatment should always be directed toward the primary pathology and the clinical presentation. In chronic cases, surgical treatment is only palliative.