Pancreatic adenocarcinoma is currently one of the deadliest cancers with high mortality rate. This disease leads to an aggressive local invasion and early metastases and is poorly responsive to treatment with chemotherapy or chemoradiotherapy. Radical resection is still the only curative treatment for pancreatic cancer, but it is generally accepted that a multimodality strategy is necessary for its management. Therefore, new alternative therapies have been considered for local treatment. Chemotherapeutic resistance in pancreatic cancer is associated with a low penetration of drugs into tumor cells due to the presence of fibrotic stroma surrounding cells. In order to increase the uptake of chemotherapeutic drugs into tumor cells, electrochemotherapy can be used for treatment of pancreatic adenocarcinoma leading to an increased tumor response rate. In clinical practice, no side effects or major complications have been recorded after electrochemotherapy of locally advanced pancreatic tumors, nor damages to surrounding viscera that required medical or surgical treatment. The patients reported pain reduction immediately after electrochemotherapy, compared to preoperative status and better quality of life. However, until now there is still the question of how to monitor the response. The only morphologic data obtained by computed tomography (CT) or magnetic resonance (MR) imaging were not able to discriminate between responding and nonresponding patients. The changes in functional data, obtained with positron emission tomography (PET), MR, and CT study, and the correlation of these, could be more suitable to assess electrochemotherapy response.