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Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterized by an impairment of coordinated propulsive activity in the gastrointestinal (GI) tract, which clinically mimics mechanical intestinal obstruction. CIPO is the most severe and debilitating form of GI dysmotility. CIPO may be primary or be secondary to pathology at any level of the brain-gut axis as well as systemic disease. The clinical features of CIPO are pleomorphic and largely depend on the site and extent of the segment of the GI tract involved. The diagnostic approach includes the need for investigations to exclude mechanical GI obstruction, screening for causes of secondary CIPO and the identification of the disease phenotype as well as the prompt recognition and treatment of complications such as malnutrition and small intestinal bacterial overgrowth. In managing this disorder, a holistic, multidisciplinary approach is needed with judicious use of pharmacotherapeutic agents. While currently there are no specific therapeutic modalities for CIPO, treatment is largely directed at maintaining adequate nutrition and electrolyte balance and enhancing coordinated GI motility. Surgery should be avoided unless advisable for carefully selected patients and may include stoma formation. This narrative review provides a concise overview of the literature on this rare, severe and complex disorder, and highlights the need and areas for further research to improve both diagnostics and therapeutics.