Fluid resuscitation plays a fundamental role in the treatment of septic shock. Administration of inappropriately large quantities of fluid may lead to volume overload, which is increasingly recognized as an independent risk factor for morbidity and mortality in critical illness. In the early treatment of sepsis, timely fluid challenges should be given to optimize organ perfusion, but continuous positive fluid balance is discouraged. In fact, achievement of a negative fluid balance during treatment of sepsis is associated with better outcomes. This review will discuss the relationship between fluid overload and unfavorable outcomes in sepsis, and how fluid overload can be prevented and managed.