Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) continue to play an increasing role in the management of peritoneal surface malignancies of gastrointestinal origin. The prognosis of patients and the responses to cytoreductive surgery and HIPEC depend on the histology, the degree of malignant transformation, the adequacy of the cytoreductive surgery, and the response to systemic therapy. Continuous interaction between medical and surgical oncologists is needed to identify the most appropriate patients for and the most efficient sequence of the available therapeutic modalities.