The first medical application of electroporation was used for introducing poorly permeant anticancer drugs into tumor nodules. Soon also gene electrotransfer became of special interest because of its low cost, easiness of realization and safety. Namely, viral vectors can have serious limitations in terms of immunogenicity and pathogenicity when used for DNA transfer.
Irreversible electroporation is being used and evaluated as cardiac ablation therapy to kill very small areas of heart muscle. This is done to treat irregularities of heart rhythm. A cardiac catheter  delivers trains of high-voltage ultra-rapid electrical pulses that form irreversible pores in cell membranes, resulting in cell death. It is thought to allow better selectivity than the previous techniques, which used heat or cold to kill larger volumes of muscle.
A higher voltage of electroporation was found in pigs to irreversibly destroy target cells within a narrow range while leaving neighboring cells unaffected, and thus represents a promising new treatment for cancer, heart disease and other disease states that require removal of tissue. Irreversible electroporation (IRE) has since proven effective in treating human cancer, with surgeons at Johns Hopkins and other institutions now using the technology to treat pancreatic cancer previously thought to be unresectable.
Also first phase I clinical trial of gene electrotransfer in patients with metastatic melanoma was reported.  Electroporation mediated delivery of a plasmid coding gene for interleukin-12 (pIL-12) was performed and safety, tolerability and therapeutic effect were monitored. Study concluded, that gene electrotransfer with pIL-12 is safe and well tolerated. In addition partial or complete response was observed also in distant non treated metastases, suggesting the systemic treatment effect. Based on these results they are already planning to move to Phase II clinical study. There are currently several ongoing clinical studies of gene electrotransfer where safety, tolerability and effectiveness of immunization with DNA vaccine, which is administered by the electric pulses is monitored.
Although the method is not systemic, but strictly local one, it is still the most efficient non-viral strategy for gene delivery.