Following the discovery of Helicobacter pylori, the last decade has seen major advances in our understanding of gastroduodenal disease. However, our knowledge remains incomplete and the exact mechanism by which H. pylori causes inflammation and ulceration is still not known. The role of H. pylori in relation to other well known risk factors for gastroduodenal disease such as diet, smoking and the use of non-steroidal anti-inflammatory drugs is also unclear. Free radicals are highly toxic chemical species and evidence presented in this review suggests that they play an important role in the pathophysiology of gastroduodenal disease caused by many risk factors, including H. pylori. Dietary antioxidant deficiency may be a major factor in the development of gastric cancer and may exacerbate the carcinogenesis of nitrosamines. Antioxidant deficiency, either dietary or secondary to increased requirements as in smoking, may be a factor in the development of disease following H. pylori infection. The time now appears to be ripe for studies of novel antioxidant therapeutic strategies for gastroduodenal disease.