Functional gastrointestinal disorders (FGIDs) are common and currently defined by a symptom-based classification with no discernable pathology. In functional dyspepsia (FD), the duodenum is now implicated as a key area where symptoms originate.This is attributed to immune activation with increasing evidence indicating a role for duodenal eosinophilia. In irritable bowel syndrome (IBS), mastocytosis has been documented throughout the small and large intestine. Eosinophils and mast cells are an important link between innate and adaptive immunity, and are important in allergic type TH2 inflammation. Eosinophils may give rise to symptoms due to release of preformed cytokine proteins, which trigger neural excitation, muscle spasm, and pain. The close relationship of mast cells to nerves in IBS may similarly give rise to symptoms. Genetic studies also support of the role of innate immunity in FGIDs. The data supporting a prime role for eosinophils and mast cells in subsets of FD and IBS has become credible, and these data should be used to implement advances in diagnosis and therapeutic trials.