The successful translation of promising research findings from basic research laboratories into useful clinical products for the management of septic patients has proven to be a daunting challenge. The complexity and variability of the clinical entity referred to as sepsis makes it intrinsically difficult to model preclinical systems and predict efficacy of potentially useful, experimental, therapeutic agents. Technological innovations in microarrays, microfluidics, and nanotechnology make it feasible to study the evolution of sepsis in small animal models in considerable detail. The recognized limitations of standard preclinical platforms used to study sepsis have lead to innovative approaches to study sepsis in silico, and in more complex and clinically more valid ex vivo tissue perfusion models and animal systems. It is abundantly clear that sepsis researchers need to do a better job informing clinicians about the possible benefits and potential risks of new treatment interventions as they traverse the gap between the bench and the bedside.