Oxygen-derived free radicals are now considered important contributors to tissue injury associated with ischemia and reperfusion. Transition metals, primarily iron, greatly enhance the generation of these active species, which can destroy a large variety of biomolecules, in particular the lipid components of cell membranes. This review tries to demonstrate why cardiopulmonary bypass and aortic cross-clamping are situations that predispose to oxygen free radical production, and how "anti-free radical" agents such as enzymatic scavengers, antioxidants, and iron chelators may prove to be useful therapeutic adjuncts in the clinical setting of open heart surgery.