Malignant mesothelioma is an uncommon and usually fatal cancer, for which there is no standard treatment. However, surgical resection remains the mainstay of treatment because of the inability to treat the entire hemithorax effectively with radiation and the lack of effective chemotherapy drugs. Extrapleural pneumonectomy is the only technically feasible operation for patients who have bulky local tumor and chronic entrapment of the lung, but pleurectomy/decortication is associated with a lower operative morbidity and mortality, and seems to lead to an equally good survival in patients who have early-stage disease. Because of the high risk of local recurrence after surgical resection by either extrapleural pneumonectomy or pleurectomy/decortication, efforts have been directed at developing effective adjuvant treatment. Radiation given postoperatively after pleurectomy/decortication has led to a minimal improvement in survival and to significant side effects. Adjuvant chemotherapy is considered investigational but is currently being evaluated in a clinical trial using high-dose intrapleural and systemic chemotherapy after pleurectomy/decortication. Additional well-designed prospective trials are needed to alter the dismal outcome of this disease.