Electroporation and the associated phenomenon of electrofusion have been widely adapted as tools to a broad range of biomedical research and therapy. In this article, we summarize our adaptation of the electroporation and electrofusion technology in two fronts of cancer research and treatment. The first is genetic manipulation of hematopoietic cells for the purpose of cancer treatment. High efficiency transfection methods have been developed to transfect NK cells, peripheral blood stem cells, and bone marrow derived dendritic cells. Hybrids of tumor cells and bone marrow derived dendritic cells have been formed by electrofusion for the purpose of tumor vaccines. The second front is the use of transcutaneous electroporation to deliver anticancer drugs and vaccines across the skin. Methods to extend the upper molecular weight limit of transcutaneous electroporation have been developed. The pro-photosensitizer drug, delta-amino levulinic acid, the anticancer drug methotrexate, and peptide vaccines designed for cancer prevention and immunotherapy have been delivered transcutaneously by electroporation. These studies hold promise for the treatment of cancers in human.