The lower oesophageal sphincter (LOS) is a specialized segment of the circular muscle layer of the distal oesophagus, accounting for approximately 90% of the basal pressure at the oesophago-gastric junction. Together with the crural diaphragm, it functions as an antireflux barrier protecting the oesophagus from the caustic gastric content. During swallowing or belching, the LOS muscle must relax briefly in order to allow passage of food or intragastric air. These swallow-induced and prolonged transient lower oesophageal sphincter relaxations (TLOSRs) respectively result from activation of the inhibitory motor innervation of the sphincter. Both in man and animals, the main neurotransmitter released by the inhibitory neurones is nitric oxide. The two typical examples of dysfunction of the LOS are achalasia and gastro-oesophageal reflux disease (GORD). Achalasia is characterized by reduction or even absence of the inhibitory innervation to the LOS, leading to impaired LOS relaxation with dysphagia and stasis of food in the oesophagus. On the contrary, GORD results from failure of the antireflux barrier, with increased exposure of the oesophagus to gastric acid. This leads to symptoms such as heartburn and regurgitation, and in more severe cases to oesophagitis, Barrett's oesophagus and even carcinoma. To date, TLOSRs are recognized as the main underlying mechanism, and may represent an important target for treatment. More insight in the pathogenesis of both diseases will undoubtedly lead to new treatments in the near future.