Helicobacter pylori infection is linked to conditions of the upper gastrointestinal tract, including peptic ulcer and gastric adenocarcinoma. It has also been associated with a wide variety of non-gastrointestinal tract conditions. However, the evidence in support of H. pylori infection as a cause of the non-gastrointestinal tract conditions is not widely understood. We reviewed the medical literature for publications and abstracts dealing with putative non-gastrointestinal tract associations of H. pylori infection. We appraised the level of evidence and applied it to an established set of 9 criteria for determining causation. We found that many studies examining a possible causal relationship have been uncontrolled or inadequately controlled. Studies have often failed to control for socioeconomic status. Studies of treating H. pylori infection in patients with these disorders have been poorly designed and inappropriately controlled, and therefore add little to the evidence base. Attention should be focused on appropriate testing for and treatment of H. pylori infection in patients with conditions that are of proven association, notably peptic ulcer disease.