Electroporation is a novel therapeutic modality that uses pulsed electrical currents to enhance the uptake of drugs, vaccines and genes into cells, and has been used for over 20 years. Electroporation therapy using cytotoxic drugs is called electrochemotherapy. Electrochemotherapy has been studiedin vitro, in vivoand in clinical trials. It is potentially useful for treating patients with metastatic tumors, such as melanoma, and even select primary tumors, such as head and neck squamous cell carcinomas and basal cell carcinoma. Various chemotherapeutic agents have been tested with electroporation therapy, but bleomycin and cisplatin are the two most widely used. The biological basis of electroporation therapy is outlined in this review and basic science studies and the limited clinical studies that have involved electrochemotherapy are reviewed. Particular focus is placed on trials involving melanoma, head and neck cancers and other primary and metastatic skin cancers.