The peritoneal malignancies span the biologic spectrum of aggressiveness from the indolent growth pattern and superficial nature of well-differentiated mucinous appendiceal adenocarcinoma to the rapidly growing and invasive nature of poorly differentiated signet ring cell adenocarcinomas of the appendix, colon, and stomach. An understanding of the biology, distribution, and volume of disease is critical to appropriately selecting patients for cytoreduction and HIPEC with the goal of long-term survival. Herein the authors discuss appropriate the evaluation and selection of patients for with peritoneal surface malignancies for cytoreduction and HIPEC.