In their effort to characterize the systemic "off-target" effects of radiofrequency (RF) ablation and irreversible electroporation (IRE), Bulvik et al demonstrated substantial differences in physiologic, tumorigenic, and immunologic responses between the two ablative modalities. By establishing that IRE may in fact stimulate more robust inflammatory and systemic reactions than RF at liver ablation, the authors conclude that the selection of a given ablation energy source may alter the clinical outcome depending on the circumstance-both favorably and unfavorably.