Sleep dysfunction is an epidemic affecting a large portion of the adult population. Recent studies have linked sleep dysfunction with an upregulation of proinflammatory cytokines (eg, tumor necrosis factor-α, interleukin-1 and interleukin-6), the implications of which can have a profound impact on a variety of gastrointestinal disease. In particular, sleep dysfunction seems to accelerate disease states characterized by inflammation (eg, gastroesophageal reflux disease, irritable bowel syndrome and functional dyspepsia, chronic liver disease, inflammatory bowel disease, and colorectal cancer). This article evaluates the complex interplay between sleep dysfunction and gastrointestinal health and disease.