The gastrointestinal (GI) system is responsible for the digestion and absorption of ingested food and liquids. Due to the complexity of the GI tract and the substantial volume of material that could be covered under the scope of GI physiology, this chapter briefly reviews the overall function of the GI tract, and discusses the major factors affecting GI physiology and function, including the intestinal microbiota, chronic stress, inflammation, and aging with a focus on the neural regulation of the GI tract and an emphasis on basic brain-gut interactions that serve to modulate the GI tract. GI diseases refer to diseases of the esophagus, stomach, small intestine, colon, and rectum. The major symptoms of common GI disorders include recurrent abdominal pain and bloating, heartburn, indigestion/dyspepsia, nausea and vomiting, diarrhea, and constipation. GI disorders rank among the most prevalent disorders, with the most common including esophageal and swallowing disorders, gastric and peptic ulcer disease, gastroparesis or delayed gastric emptying, irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Many GI disorders are difficult to diagnose and their symptoms are not effectively managed. Thus, basic research is required to drive the development of novel therapeutics which are urgently needed. One approach is to enhance our understanding of gut physiology and pathophysiology especially as it relates to gut-brain communications since they have clinical relevance to a number of GI complaints and represent a therapeutic target for the treatment of conditions including inflammatory diseases of the GI tract such as IBD and functional gut disorders such as IBS.