Neutropenic enterocolitis (NE) is a life-threatening complication associated with neutropenia and the main cause of acute abdominal syndrome in neutropenic patients, especially those receiving intensive chemotherapy. This review aims to delineate actual insights into this clinical entity, to emphasize diagnostic and therapeutic management, and to generate hypotheses on pathophysiology to identify avenues for research. Diagnosis is based on the association of neutropenia, fever, abdominal symptoms, and radiologic bowel wall thickening. Main complications are sepsis, perforations, and gastrointestinal bleeding. Several mechanisms may be responsible for mucosal injury: treatment-induced necrosis of the intestinal specific infiltrates, spontaneous intramural hemorrhage, or microvascular thrombosis. The prevailing cause is the direct cytotoxicity of chemotherapy. However, the role of gut dysbiosis in NE remains to be fully elucidated. Therapeutic management includes early multidrug antibiotherapy, transfusion support, hematopoietic growth factor treatment, fluid resuscitation, correction of electrolytes imbalance, and bowel rest. Indication and timing for surgical management are still debated.