For decades, interactions between the enteric neuromuscular apparatus and the central nervous system have served as the primary focus of pathophysiological research in the functional gastrointestinal disorders. The accumulation of patient reports, as well as clinical observations, has belatedly led to an interest in the role of various luminal factors and their interactions with each other and the host in functional gastrointestinal disorders. Most prominent among these factors has been the role of food. As a consequence, while not always evidence-based, dietary interventions are enjoying a renaissance in irritable bowel syndrome management. Not surprisingly, given its exploration in many disease states, the gut microbiota has also been studied in functional gastrointestinal disorders; data remain inconclusive. Likewise, there is also a considerable body of experimental and some clinical data to link functional gastrointestinal disorders pathogenesis to disturbances in epithelial barrier integrity, abnormal entero-endocrine signaling and immune activation. These data provide growing evidence supporting the existence of micro-organic changes, particularly in subgroups of patients with functional dyspepsia and IBS. However, their exact role in the complex pathophysiology and symptom generation of functional gastrointestinal disorders needs to be further studied and elucidated particularly with longitudinal and interventional studies.