The ability of the p-stacked array of heterocyclic DNA bases to behave as an efficient conduit for charge migration has been explored using a wide array of experimental approaches. Spectroscopic studies and biochemical assays show that charge transfer through well-stacked DNA can be extremely facile, although sensitive to structural distortions within the DNA base stack. The efficiency of these long-range reactions depends upon the coupling of the electron donor, acceptor and intervening base pairs within the base stack. As a result, base mismatches and stacking disruptions associated with protein binding to the helix can significantly perturb long range charge transfer. DNA-protein interactions which result in the base flipping of a nucleotide out of the DNA p-stack, in particular, dramatically inhibit long-range charge transfer through DNA. Whether these reactions that can occur over large molecular distances, be applied in sensing DNA damage, and be modulated by DNA-binding proteins, are exploited within the cell remains to be determined.