Malignant pleural mesothelioma (MPM) is an uncommon neoplasm arising from mesothelial cells of the pleura. The prognosis is poor with a median survival of 8 to 18 months after diagnosis. Multimodality regimens combining chemotherapy, radiotherapy, immunotherapy, and surgery are being used more frequently in patient management. Extrapleural pneumonectomy is the surgical treatment of choice in 10% to 15% of patients who present with resectable disease and is reported to prolong survival. Accurate staging is important to distinguish patients who are resectable from those requiring palliative therapy. Integrated computed tomography-positron emission tomography (CT-PET) increases the accuracy of overall staging in patients with MPM and significantly improves the selection of patients for curative surgical resection. Specifically, CT-PET detects more extensive disease involvement than that shown by other imaging modalities and is particularly useful in identifying occult distant metastases. This article reviews aspects of imaging performed in the initial staging of patients with MPM according to the International Mesothelioma Interest Group staging system and will emphasize the appropriate role of CT-PET imaging in determining the T, N, and M descriptors.