Free-radicals play an important role in the pathogenesis of many diseases, accounting for continuing interest in the identification and development of novel antioxidants that prevent radical-induced damage. To develop more-powerful weapons that address complex diseases in which free-radicals might be significant, but not exclusive drivers, antioxidants that also have other pharmacological effects are desired. To obtain multipotent antioxidants, one can screen drug collections and/or natural-product libraries, or couple an antioxidant group with other pharmacophores. It is interesting to note that most rationally designed multifunctional antioxidants are structurally different from their naturally occurring counterparts. Therefore, nature's design strategy provides important clues as to how the design concept for multipotent antioxidants can be improved.