The thoracic cavity contains numerous tissue types from which tumors may arise. Broadly speaking, the cavity is comprised of the pleural surfaces, the mediastinum and its enclosed viscera, and the lungs. Neoplasms arising from these structures are frequently advanced at the time of diagnosis, and surgery is rarely curative for malignant processes. Although reports describing anticancer chemotherapy use in dogs and cats for tumors of the thoracic cavity largely have been anecdotal, as advances are made in the chemotherapeutic management of comparable tumors in human cancer patients and as veterinarians become familiar with these compounds, use of antineoplastics as an adjunct to, or in place of, local treatment modalities should increase. This article reviews the epidemiology, clinical features, and diagnosis of pulmonary neoplasia; mediastinal neoplasia, particularly thymoma; and pleural neoplasia, with emphasis on mesothelioma. In addition, options for chemotherapy, derived from both the human and veterinary literature, are given for each tumor type.