The affinity of metal ions for DNA is logical considering that the structure of DNA includes a phosphate backbone with a net-negative charge, a deoxyribose sugar with O atoms, and purine and pyrimidine bases that contain O and N atoms. DNA-metal ion interactions encompass a large area of research that ranges from the most fundamental characterization of DNA-metal ion binding to the role of DNA-bound metal ions in disease and human health. Alternative DNA base pairing mediated by metal binding is also being investigated and manipulated for applications in logic gates, molecular machines, and nanotechnology. This review highlights recent work aimed at understanding interactions of redox-active metal ions with DNA that provides a better understanding of the mechanisms by which various types of oxidative DNA damage (strand breakage and base modifications) occur. Antioxidants that mitigate oxidative DNA damage by coordinating metal ions that produce reactive oxygen species are addressed, as well as recent work on the effect of DNA-metal ion interactions and the efficacy of quinolone-based antibacterial drugs. Recent advances in metal-mediated base pairing that triggers conformational changes in DNA structure for use as selective metal ion sensors and novel nanotechnology applications are also included.