In the last years the need for a non-invasive diagnostic tool that would help to discriminate between organic and functional gastrointestinal disorders directed research towards potential immunological markers. A great number of non-invasive bio-markers has been proposed, including eosinophilic cationic protein, elastase, esterase, myeloperoxidase, lysozyme, lactoferrin, and calprotectin. Compared to other biomarkers, calprotectin (also called MRP8/14, calgranulin A/B , S100 A8/A9) may offer advantages based on its biological characteristics. Calprotectin is a 36.5-kDa, calcium and zinc binding polypeptide which constitutes about 60% of soluble cytosol proteins in human neutrophils. It is also found in monocytes, keratinocytes, muscle tissue and infiltrating tissue macrophages. When bound to calcium it becomes resistant to proteolysis and colonic bacterial degradation. This make is stable for up to 1 week at room temperature and facilitate its determination in feces. Calprotectin is involved in the regulation of the inflammatory process, participate to the early innate immune response and exert antimicrobial, anti-proliferative and apoptotic properties. Fecal calprotectin is a direct measure of mucosal inflammation activity and becomes detectable when intestinal inflammation is still at an insufficient level to cause an increase in serum inflammation markers. In the last decade fecal calprotectin has been proposed as a marker to rule out acute and chronic intestinal inflammatory diseases in children with typical gastrointestinal symptoms. Many studies demonstrated its diagnostic utility in identifying children and adults with inflammatory bowel disease and correlate with the degree of disease activity. The detection of elevated levels of fecal calprotectin in healthy infants during the first few weeks of age, limits their use as screening test for intestinal inflammatory diseases in early life. Despite this evidence, the measurement of calprotectin in the serum has been proposed to identify neonates with necrotizing enterocolitis. Recent studies have shown higher fecal calprotectin levels in infants with irritable bowel syndrome and colics, compared with healthy controls. Additionally, a correlation was found between fecal calprotectin concentration and IBS clinical presentation severity. However, these studies do not provide data on diagnostic accuracy in distinguish between organic and functional gastrointestinal disorders. Despite significant limitations, these evidences suggest the presence of a subtle inflammatory process underlying functional gastrointestinal disorders and open new perspectives on their pathogenesis. Fecal calprotectin may play a role that could be revealed in further, specifically designed, studies. Changes in microflora, permeability, calprotectin excretion and other inflammatory biomarkers, should be investigated to clarify if a continuum exists between inflammatory conditions and intestinal functional diseases.