Cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy is an aggressive, potentially curative approach used to treat locoregional disease associated with primary and secondary malignancies of the peritoneum. It involves resection of all macroscopic disease larger than 2.5 mm, followed by instillation of hyperthermic chemotherapy directly into the peritoneum for higher drug exposure to microscopic disease. In select patients with primary peritoneal mesothelioma, pseudomyxoma peritonei, colorectal adenocarcinoma, appendiceal adenocarcinoma, or ovarian cancer, with no extra-abdominal metastasis and limited involvement of the peritoneum, the procedure can be performed to increase overall survival.