An aggressive approach to peritoneal dissemination involves peritonectomy procedures combined with preoperative intraperitoneal chemotherapy, intraoperative chemo-hyperthermia, and postoperative systemic chemotherapy. We have been performing multimodal therapy consisting of peritonectomy plus perioperative chemotherapy for the treatment of patients with peritoneal dissemination. Fifty-seven patients with established peritoneal dissemination from gastric cancer (n = 32), colon cancer (n = 17), ovarian cancer (n = 7), and mesothelioma (n = 1) have been treated with peritonectomy and intraoperative chemo-hyperthermia. Five-year survival rates of patients with gastric and colon cancer were 18% and 38%, respectively. Among various clinical factors, complete tumor resection was the most significant prognostic factor, and the prognosis of patients who underwent complete cytoreduction was significantly better than those who received incomplete cytoreduction. A multimodal therapy consisting of perioperative chemotherapy and peritonectomy with complete cytoreduction may be the most powerful method to treat patients with established peritoneal dissemination.