Copper ions are well suited to facilitate formation of reactive oxygen species (ROS) that can damage biomolecules, including DNA and chromatin. That this can occur in vitro with isolated DNA or chromatin,or by exposure of cultured mammalian cells to copper complexed with various agents, has been well demonstrated. Whether that is likely to occur in vivo is not as clear. This review addresses the question of whether and how copper ions or complexes – in forms that could be present in vivo, damage DNA and chromosome structure and/or promote epigenetic changes that can lead to pathology and diseases, including cancer and neurological conditions such as Alzheimer's disease, Lewy body dementias, and spongiform encephalopathies. This question is considered in light of our knowledge that copper-dependent enzymes are important contributors to antioxidant defense, and that the mammalian organism has robust mechanisms for maintaining constant levels of copper not only in body fluids but in its major organs. Overall,and except in unusual genetic states that lead to copper overload in specific cells (particularly those in liver), it appears that excessive intake of copper is not a significant factor in the development of disease states.