Fluid resuscitation continues to be recommended as the first-line resuscitative therapy for all patients with severe sepsis and septic shock. The current acceptance of the therapy is based in part on long history and familiarity with its use in the resuscitation of other forms of shock, as well as on an incomplete and incorrect understanding of the pathophysiology of sepsis. Recently, the safety of intravenous fluids in patients with sepsis has been called into question with both prospective and observational data suggesting improved outcomes with less fluid or no fluid. The current evidence for the continued use of fluid resuscitation for sepsis remains contentious with no prospective evidence demonstrating benefit to fluid resuscitation as a therapy in isolation. This article reviews the historical and physiological rationale for the introduction of fluid resuscitation as treatment for sepsis and highlights a number of significant concerns based on current experimental and clinical evidence. The research agenda should focus on the development of hyperdynamic animal sepsis models which more closely mimic human sepsis and on experimental and clinical studies designed to evaluate minimal or no fluid strategies in the resuscitation phase of sepsis.