Gastroesophageal reflux disease (GERD) can be described as a clinical picture resulting from the reflux of stomach contents into the esophagus. The actual prevalence of GERD remains unestablished, although this disorder is generally common in old patients, male sex and in subsets of patients with pulmonary manifestations such as asthma. From a pathophysiological stand-point, GERD is thought to have a multifactorial etiology which involves genetics, anatomical, functional, environmental, hormonal and pharmacological factors. GERD has different clinical presentations which may be divided in three main classes: typical symptoms (heartburn and regurgitation); atypical or extraesophageal symptoms (angina-like chest pain, asthma, chronic cough and laryngitis); and complications (ulcers, strictures and Barrett's esophagus). In GERD diagnosis a key role is played by: accurate symptom evaluation, response to proton pump inhibitors and, finally, at least one in a life-time endoscopy. Moreover, barium swallow X-ray, 24-h esophageal pH monitoring and gastro-esophageal manometry can be useful to support diagnosis in some unusual cases or in cases partially or unresponsive to standard pharmacologic treatment.