Dyspepsia or indigestion is one of the most common disorders that is managed by general practitioners and gastroenterologists. Non-ulcer dyspepsia can be defined as upper abdominal pain or nausea in patients in whom endoscopy reveals no evidence of peptic ulceration or gastric cancer. Non-ulcer dyspepsia is a heterogeneous disorder and can be the result of such diverse entities as the irritable bowel syndrome, duodenitis or gastro-oesophageal reflux, or may be idiopathic ("essential" dyspepsia). This review traces the development of modern thought on dyspepsia and non-ulcer dyspepsia, from the 16th century to the present.