Neutropenic colitis is a complication of the treatment of hematologic malignancies and, less commonly, of other disease entities. The septic, inflammatory process has a predilection for the terminal ileum and right colon. While the pathogenesis is not clear, mucosal injury caused by several different mechanisms and local opportunistic infection play significant roles. An association has been recognized between neutropenic colitis and sepsis caused by C. septicum. Patients present with fever, diarrhea, and acute abdominal pain and tenderness often localized in the right lower quadrant. Sonography and CT are helpful in demonstrating colonic wall thickening and pericolic fluid. Peritoneal lavage has been used to exclude perforation in these critically ill patients. Although there has been debate about whether medical or operative management is best, the optimal initial therapy includes supportive care with gastric decompression, fluid and blood product replacement, and broad-spectrum antibiotics. The indications for surgery include continued intestinal bleeding despite correction of coagulopathy and pancytopenia, free intraperitoneal air, and uncontrolled sepsis. At operation, a right colectomy with ileostomy and mucous fistula or, in selected patients, primary anastomosis is the procedure of choice. Timely return of functioning neutrophils and the eventual prognosis of the primary disease are crucial to the overall success or failure of treatment of neutropenic colitis.