Electrochemotherapy is an anticancer treatment inducing uptake of chemotherapeutics by electroporation. This treatment is increasingly being used clinically and further investigations for improvement of the treatment and discovery of new drugs are ongoing. The most commonly used drugs in electrochemotherapy are bleomycin and cisplatin, but many other chemotherapeutic drugs have been tested in vitro and in vivo. Drugs with an anticancer effect such as radioactive compounds and calcium have also been tested in combination with electroporation. Different aspects have to be considered when investigating possible new drugs in combination with electroporation, such as the properties of the drug and whether electroporation can increase the uptake of the drug, as well as the effect of the treatment on normal cells and tissue. In this chapter some of the drugs tested in combination with electroporation are described followed by a broader description of a new drug that has recently been investigated, calcium. Here we describe the process from idea over in vitro and in vivo experiments to clinical trial. The results showed that calcium electroporation is effective in inducing cell death in vitro and tumor necrosis in vivo, and very interestingly it has also been shown that normal cells are less sensitive to the treatment than cancer cells. The effect of this potential novel anticancer treatment is also investigated in a clinical trial for treatment of cutaneous metastases, and calcium could be a new drug for electroporation-based therapy.