Chronic intestinal pseudo-obstruction is a severe, often unrecognized disease characterized by disabling and potentially life-threatening complications over time. The diagnosis is based on the evidence of typical clinical manifestations, radiological evidence of distended bowel loops with air-fluid levels, and the exclusion of any organic obstruction of the gut lumen. The radiological sign of intestinal occlusion allows the distinction from enteric dysmotility, which is characterized by better outcomes. Manometry can play a supportive role in defining the diagnosis, and differences in the manometric pattern of chronic intestinal pseudo-obstruction and enteric dysmotility have been shown. The disease is often unrecognized, and the diagnosis, therefore, delayed by several years. Thus, the majority of patients undergo useless and potentially dangerous surgeries. Long-term outcomes are generally poor despite surgical and medical therapies characterized by disabling and potentially life-threatening complications over time. A substantial percentage of patients requires parenteral nutrition. Failure of this nutritional support represents an indication for small bowel transplantation.