Pathological processes and disease entities in the upper gastrointestinal (GI) tract, specifically those of the oesophagus and the stomach in infancy, have received a disproportionately small amount of attention until recently when appreciation of their pathophysiology and concordant importance in terms of symptomatology has been highlighted. This is probably a phenomenon secondary to improved diagnostic yield from the recent technical advances in areas such as infant endoscopy and a shift in opinion regarding the pathophysiological origin of ubiquitous symptoms of infancy such as feeding disorders, colic and irritability. In addition, the apparently complex interactions of various aetiological factors such as pH-independent gastro-oesophageal reflux (GOR), cow's milk protein intolerance (CMPI), Helicobacter pylori gastritis and upper GI motor disorders have in the past 1-2 years become underlined in terms of aetiopathogenesis and have radically changed thinking regarding diagnosis and therapy of infants with apparent upper-GI-associated symptoms. The contribution to comprehension of infant upper GI disorders of inflammatory paradigms and ontogeny of the upper GI tract is also a recent area worthy of mention. The recent advances in all of these areas and their contribution to the understanding, and subsequent diagnosis and therapy, of upper GI symptoms and their explanation by way of aetiopathogenesis will be explored in this chapter.