Chronic intestinal pseudo-obstruction (CIPO) represents the most severe end of the spectrum of gut motility disorders comprising a group of rare, heterogeneous, and disabling disorders of the gastrointestinal (GI) tract characterized by absent or ineffective intestinal peristalsis. Pediatric CIPO results from developmental and pathological processes, which affect, either singly or in combination, the intrinsic or extrinsic intestinal neurons (neuropathy) and/or smooth muscle fibers (myopathy) and/or interstitial cells of Cajal (ICC) (mesenchymopathy). These processes lead to an inability of the small intestine to propel its luminal contents normally, which manifests clinically as continuous or repetitive episodes of intestinal obstruction in the absence of a defined, fixed lumen-occluding lesion, hence the term “pseudo”-obstruction. The diagnosis of CIPO can be challenging and is based on a combination of clinical, radiological, manometric, and histopathologic findings. At the current time, therapeutic strategies are limited and largely supportive, designed to optimize nutrition and reduce the frequency and severity of pseudo-obstructive episodes. Overall management is focused on alleviating symptomatology and complications, preserving function of the GI tract, and improving patients’ quality of life. The therapeutic armamentarium includes pharmacotherapy to address reversible causes, e.g., inflammation, and to stimulate motility where possible, special means of alimentation (enteral, parenteral, and, where tolerated, oral) to provide nutrition while preserving gut function, as well as surgical interventions such as formation of ostomies (i.e., gastrostomy, ileostomy) to allow “venting” and decompression of the gut. A number of novel agents may hold future promise, but at the present time, small bowel transplantation provides the only option for definitive cure with improved outcomes and survival in centers with the relevant expertise.