Refractory gastroesophageal reflux disease may affect up to one‐third of the patients that consume proton pump inhibitor (PPI) once daily. Treatment in clinical practice has been primarily focused on doubling the PPI dose, despite lack of evidence of its value. In patients who failed PPI twice daily, medical treatment has been primarily focused on reducing transient lower esophageal sphincter relaxation rate or attenuating esophageal pain perception using visceral analgesics. In patients with evidence of reflux as the direct trigger of their symptoms, endoscopic treatment or antireflux surgery may be helpful in remitting symptoms. The role of psychological interventions, as well as non‐traditional therapeutic strategies remains to be further elucidated.