Recently cytoreductive surgery of primary and secondary pleural tumors has been combined with hyperthermic intrathoracic chemotherapy perfusion (HITHOC) for better local tumor control. In comparison to simple instillation of chemotherapeutic agents into the pleural cavity, the combination of surgical resection of pleural tumors and simultaneous HITHOC seems to be a more effective treatment. Intra-operative perfusion allows an improved distribution of the drug in the pleural space and a higher local concentration of the chemotherapeutic agents in contrast to systemic chemotherapy. Additional advantages of HITHOC are a better response to chemotherapeutic agents and synergistic antineoplastic effects. A prerequisite for safe application of HITHOC is compliance with safety regulations. Due to the reduction in morbidity and mortality this new concept is a valuable alternative for selected patients who do not undergo radical resection (e.g. extrapleural pneumonectomy). HITHOC is an additional therapeutic option in the multimodal treatment of patients with primary or secondary tumors of the pleura.