Cardiotoxicity manifested as myocardial ischemia is not generally recognized as a side effect of 5-fluorouracil. However, there have been at least 35 cases reported since 1975. In only one of these cases was a somewhat detailed evaluation done to rule out underlying coronary disease. The case reported here of 5-FU cardiotoxicity included an extensive cardiac evaluation to rule out underlying coronary disease and to assess spasm. The literature on 5-FU cardiotoxicity is also reviewed, and its possible mechanisms are analyzed.