The importance of DNA formulation in safe and efficient electrogene transfer is increasingly recognized as electroporation technology enters into clinical development. A phenomenal increase in naked DNA delivery by electroporation offers new opportunities for nonviral gene therapies previously considered difficult because of insufficient delivery. However, significant tissue damage related to harsh electroporation conditions raises serious safety concerns with the use of electroporation in healthy tissues, which limits its current applications to only nonhealthy tissues such as tumors. DNA formulations designed to minimize tissue damage or enhance expression at weaker electric pulses have been examined to address these concerns. These include formulations fortified with the addition of transfection reagent(s), membrane-permeating agents, tissue matrix modifiers, targeted ligands, or agents modifying electrical conductivity or membrane stability to enhance delivery efficiency or reduce tissue damage. These advancements in DNA formulation could prove to be useful in improving the safety of electroporation protocols for human applications.