Chronic intestinal pseudo-obstruction (CIPO) is a syndrome defined by the presence of chronic intestinal dilation and dysmotility in the absence of mechanical obstruction or gross inflammatory disease. Specific diseases may affect any level of the brain-gut axis. For most patients, the diagnosis relies upon a combination of historical, laboratory, manometric and histological features. Recent advances into the autoimmune nature of etiologies such as Chagas' disease and paraneoplastic dysmotility and into the genetic basis of mitochondrial neurogastrointestinal encephalomyopathy, multiple endocrine neoplasia IIB and Hirschsprung's disease have greatly refined our understanding and diagnosis of these disorders. At present, medical therapy of CIPO remains limited. Current and future developments in pharmacologic agents targeting specific enteric neurotransmitters and motility patterns hold much promise for improving the care of the patients afflicted with this complex and often debilitating syndrome.