- OBJECTIVES: To discuss theoretical and practical aspects relating to the design of animal studies investigating the efficacy of novel therapeutic agents for the treatment of sepsis, and to make explicit the process whereby these studies can be evaluated for the purpose of designing clinical trials in humans. DATA SOURCES: Relevant articles from the pertinent literature were reviewed. STUDY SELECTION: Studies relevant to an evidence-based assessment of clinical studies on therapeutic efficacy, and studies relevant to the design of animal models of sepsis were selected. DATA EXTRACTION: Concepts relevant to an evidence-based assessment of the animal literature were extracted. DATA SYNTHESIS: Articles were reviewed and an evidence-based framework for the assessment of animal studies was developed. In this process, we discuss the steps that are necessary to assess the internal validity of an individual study and review topics relevant to the application of animal data to the design of clinical trials. CONCLUSIONS: The success of clinical trials of sepsis therapies is predicated on the generation and interpretation of sound preclinical data. In this review, we have attempted to outline an evidence-based approach to the assessment of preclinical animal studies evaluating novel therapeutic interventions in sepsis.