Colorectal cancer recurrence may be conceptualized as resulting from two entirely different mechanisms. First, metastases through endothelial-lined channels occur to both lymphatic and hematogenous routes. The cancers that disseminate in this fashion are metastatically inefficient. This dissemination occurs before the surgical resection of the primary cancer. Second, full thickness penetration of cancer through the bowel wall or, more frequently, intraperitoneal tumor emboli caused by the trauma of surgery result in implantation recurrence. This is seen at the resection site and on peritoneal surfaces. For the most part, this dissemination occurs at the time of surgical resection of the primary cancer. By changing the route (intraperitoneal vs. systemic) and timing (early postoperative vs. adjuvant) of chemotherapy administration this second mechanism of surgical treatment failure may be prevented. Phase II and pharmacologic studies suggest that improved survival and quality of life may occur with optimal use of early postoperative intraperitoneal chemotherapy.