Background: Bioelectrics, an interesting new area of medicine, combines pulsed high-voltage engineering with cell biology and has many potential applications. Pulsed electric current can be used to produce irreversible electroporation (IRE) of cell membranes with resulting cell death. This process has been shown to ablate tumors in animal studies. Methods: A clinical trial of IRE as a tumor ablation therapy was performed at our institution. A pulsating direct current of 20 to 50 A and 500 to 3000 V was delivered into metastatic or primary tumors in the liver, kidney, or lung via needle electrodes inserted under computed tomography (CT) or ultrasound guidance. Patients required a relaxant general anesthetic. We describe some challenges presented to anesthesiologists. Guidelines for anesthesia were produced and modified as issues became apparent. The patients' charts were audited throughout. Results: We noted a number of issues. The electrical discharge produced generalized upper body muscular contractions requiring neuromuscular blockade. Two patients developed positional neuropraxia because of the extended arm position requested for CT scanning. After experimentation, we have developed a modified arm position. Some patients developed self-limiting ventricular tachycardias that are now minimized by using an electrocardiogram synchronizer. Three patients developed pneumothoraces as a result of the needle electrode insertion. Conclusions: Relaxant general anesthesia is required for IRE of the liver, lung, and kidney. An electrocardiogram synchronizer should be used to minimize the risk of arrhythmias. Attention to the position of the arms is required to maximize CT scan quality but minimize brachial plexus strain. Simple postoperative analgesia is all that is required in most patients.