Extensive preclinical research investigating gene electrotransfer for the treatment of multiple diseases has supported several clinical applications. Infectious disease vaccines and cancer therapies are the primary applications to have reached human trials. Regulatory requirements for clinical trials are often more substantial for biologics such as nucleic acid-based therapies than for medical devices. Clearly, gene electrotransfer for trials must achieve approval in both categories, so the transition to clinical trials commonly requires supplemental research to meet these regulatory burdens. This chapter reviews those vaccine clinical trials that have successfully demonstrated preclinical efficacy, acquired financing, negotiated for the appropriate regulatory approval and published peer-reviewed manuscripts describing clinical results. Of the four basic pathogen categories, the vast majority of vaccine trials focus on viral transmission. A single vaccine trial focused on a parasite; no trials to date have addressed bacterial or fungal pathogens. Initially, vaccine trials focused on human immunodeficiency virus and more recently on coronaviruses and other viruses often associated with outbreaks. Although several infectious disease vaccine trials showed promise based on immunological markers, true efficacy has not been directly determined. The statistical demonstration of prophylactic efficacy necessary for regulatory approval would require long-term tracking of a significant number of subjects.