Chronic intestinal pseudo-obstruction (CIPO) comprises a group of rare, heterogeneous, and disabling disorders of the gastrointestinal (GI) tract characterized by absent or ineffective intestinal peristalsis. CIPO in children results from a spectrum of developmental and pathological processes that affect, singly or in combination, the intrinsic or extrinsic intestinal nerves (neuropathy) and/or smooth muscle fibers (myopathy) and/or interstitial cells of Cajal (ICC) (mesenchymopathy). Ultimately, this leads to an inability of the small bowel to propel its luminal contents, which manifests clinically with repetitive episodes or continuous signs and symptoms of intestinal obstruction in the absence of a defined, fixed lumen-occluding lesion, hence the term “pseudo”-obstruction. The diagnosis of CIPO remains challenging and should be based on a combination of clinical, radiological, manometric, and histopathologic findings. Current therapeutic strategies are limited and mainly supportive, aimed at maintaining the patient’s optimal nutritional status and reducing the frequency and severity of the pseudo-obstructive episodes. The latter in turn should limit symptoms and complications, preserve function of the GI tract, and improve overall quality of life. This can be achieved with appropriate pharmacotherapy, enteral, and parenteral nutrition (including oral nutrition if tolerated) along with formation of ostomies (i.e., gastrostomy, ileostomy) to allow “venting” and decompression of the gut. A number of novel agents may hold 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.