Persistent symptoms despite two months of optimal treatment with a proton pump inhibitor in a patient with history of documented gastroesophageal reflux disease (GERD) is considered the definition of refractory GERD. The terms “refractory reflux-like symptoms,” and “refractory GERD” are not synonymous and may represent different types of patients. There are a multitude of causes of refractory GERD, including other esophageal disorders that may overlap with GERD. Diagnostic workup is aimed to identify underlying causes, such as persistent pathologic acid reflux, weakly acid or alkaline reflux, duodenogastroesophageal reflux, gastroparesis, and overlapping functional esophageal disorders. Management of refractory GERD begins with ensuring optimization of PPI treatment including adherence to time of administration, compliance patient’s specific lifestyle modifications. When required, further management is tailored to the underlying cause, the predominant symptom, body habitus, and presence of a large hiatal hernia. Depending on these factors, patients with refractory GERD may be treated with other antireflux medications, antireflux surgery, endoscopic therapies, neuromodulators and behavioral interventions.