DNA damage by redox-active metal complexes depends on the interaction of the metal complex with DNA together with the mechanism of oxygen activation. Weak interaction, tight binding, and direct involvement of DNA in the coordination sphere of the metal are described. Metal complexes acting through the production of diffusing radicals and metal complexes oxidizing DNA by metal-centered active species are compared. Metal complexes able to form high-valent metal-oxo species in close contact with DNA and perform DNA oxidation in a way reminiscent of enzymatic chemistry are the most elegant systems.