Neutropenic enterocolitis (NEC) is a life-threatening disease with substantial morbidity and mortality, seen primarily in patients with hematologic malignancies. The frequency of NEC has increased with the widespread use of chemotherapeutic agents such as the taxanes, which cause severe gastrointestinal mucositis. Neutropenic patients with fever and abdominal symptoms (cramping, pain, distention, diarrhea, GI bleeding), should undergo evaluation of the abdomen for bowel wall thickening of >4 mm, the hallmark of NEC. Clostridium difficile infection should be ruled out, as well as other etiologies such as graft-versus-host disease. Complications include bacteremia, which is often polymicrobial, hemorrhage, and bowel wall perforation/abscess formation. Management includes bowel rest, correction of cytopathies and coagulopathies, and broad spectrum antibiotics and antifungal agents. Surgical intervention may be necessary to manage complications such as hemorrhage and perforation and should be delayed, if possible, until recovery from neutropenia.