Gastroesophagel reflux disease (GERD) is a common condition encountered in clinical practice. Over the years there has been a continuous interaction between the understanding of the disease, the diagnostic tools and treatments of GERD. The use of proton pump inhibitor (PPI) trials by primary care physicians as diagnostic tool in patients with symptoms suspected to be due to GERD has led to a shift in the type of patients referred to specialists. Currently, gastrointestinal specialists are frequently asked to evaluate patients with persistent reflux symptoms despite acid suppressive therapy. In these patients symptoms can be associated with reflux (both acid and non-acid) or not associated with reflux. While conventional pH monitoring can quantify esophageal acid exposure and evaluate the association between symptoms and acid reflux, it cannot reliably detect reflux episodes with a pH > 4 (i.e. non-acid reflux). Detecting reflux episodes by changes in intraluminal resistance to alternating current (i.e. impedance), combined multichannel intraluminal impedance and pH (MII-pH) monitoring offers the opportunity to detect both acid and non-acid reflux episodes and to evaluate the relationship between symptoms and reflux. We believe that MII-pH monitoring has become the new ''gold standard'' for clarifying the mechanisms of persistent symptom on PPI therapy.