Treatment of NCCP remains a real challenge due to the diverse underlying mechanisms responsible for patients' symptoms. Given the fact that GERD is by far the most common etiology, proton pump inhibitor (PPI) therapy has been tried extensively; however, after 6 weeks of treatment complete resolution of symptoms occurs in only 30% of patients, the optimal duration of PPI administration is not known, while the best maintenance dose has never been determined. Although the administration of selective serotonin reuptake inhibitors (SSRIs) could theoretically benefit those patients with esophageal hypersensitivity, the trials that have been published so far have included small number of patients and reported conflicting results, while the co-administration of PPIs with SSRIs has not been evaluated so far. Furthermore, data on treatment of patients with functional chest pain are lacking.