Malignant peritoneal mesothelioma (MPM) is a rare, progressive, and ultimately fatal disease in almost all afflicted individuals. MPM is a cancer that arises diffusely from the serosa of the abdominal cavity and progresses almost exclusively in this region; understanding its characteristic tumor biology has been the reasoning behind the development of treatment strategies designed to control disease progression in the peritoneum. This principally includes operative cytoreduction and hyperthermic intra-operative perfusion of intraperitoneal chemotherapy (HIPEC). This approach has been administered either alone or in combination with early postoperative intraperitoneal chemotherapy (EPIC), or as a component of a more protracted multimodal approach employing initial debulking surgery, intraperitoneal chemotherapy, and whole abdominal radiotherapy. Median overall survivals of up to 7 years have been observed in series of patients selected for operative cytoreduction and HIPEC. Factors associated with good outcome are female gender, age less or equal to 60 years, and the ability to achieve a complete extirpation of all gross peritoneal disease. In patients with symptomatic ascites, complete palliation is achieved in almost all cases. However, this treatment strategy is not without complications and carries a morbidity of 25% and mortality up to 7%. Despite these risks, the best overall survival data have been associated with this surgical approach. At our institution, we advocate cytoreduction and HIPEC as the standard management for patients with MPM for whom operative cytoreduction appears possible and safe. We believe this treatment approach should be considered as the standard of care for patients with MPM.