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To effectively improve outcomes of septic patients, we first need to elucidate the multifaceted pathogenesis of sepsis syndromes and related inflammatory conditions. In fulfillment of such needs, in February 2016, new definitions for sepsis and septic shock were published under the acronym Sepsis-3. Although aimed at the clinical area, Sepsis-3 will have an inevitable influence upon the field of translational research as well. Sepsis-3 brings a considerable shift regarding the experimental focal point: from inflammatory states (SIRS/CARS) to organ failure (single and multiple) as the decisive factor. This shift exposes several shortcomings of the current in vivo sepsis modeling including lack of uniform scoring system for sepsis severity and organ dysfunction/failure; high variability of organ dysfunction phenotypes among animal species/strains; difficulty in reproducing severe, intensive care unit grade of organ dysfunction due to high resistance of experimental animals and others. It is intuitive that clinical Sepsis-3 should also serve as an incentive for developing a global standardized approach in sepsis modeling to maximize its translational potential. This could be achieved, for example, by generating consensus guidelines that would support scientists in their study design and optimal sepsis modeling decision-making. An implementation of such hypothetical “Minimum Quality Threshold in Preclinical Sepsis Studies” guidelines across different species has a strong potential for making sepsis studies more reliable and transpolatable. We strongly believe that an internationally coordinated standardization effort in sepsis modeling will certainly serve the above purposes well.