More than 20 years ago it was proposed that differences in body iron stores may account for differential heart disease prevalence in men and women. In 1992 Finnish investigators presented intriguing supportive evidence for this proposal by showing that middle-aged men with normal but elevated serum ferritin, a biomarker of body iron stores, were at increased risk for acute myocardial infarction. During the past dozen years many studies have followed leading to intense debate on the role of iron in the development of heart disease. A meta-analysis of prospective studies found, however, no support for the iron-heart disease hypothesis. As new disease associations with iron status continue to be explored, consideration needs to be given to the lessons learned from these studies. Moreover, additional efforts need to be made to find a simple, high throughput and more satisfactory measure of the forms of iron in the body that are liable to do damage.