The lower oesophageal sphincter (LOS) is the major component of the anti-reflux barrier. The majority of reflux episodes occur because of intermittent brief complete lower oesophageal sphincter relaxations, transient LOS relaxations, rather than from chronic absence of LOS pressure. Recent advances in the understanding of the neural mechanisms and the receptors involved in the triggering of transient LOS relaxations have provided new insights into their control and offer the potential for the development of pharmacological therapy of reflux based on control of these events. Extrinsic support by the crural diaphragm is also important and loss of this support through development of hiatus hernia significantly compromises LOS function. This chapter reviews the components of the anti-reflux barrier, the patterns and mechanisms of LOS dysfunction underlying reflux episodes, and the interplay between sphincteric and non-sphincteric factors.