Fluid boluses are a key element of hemodynamic resuscitation, but overuse of fluids also can be harmful. It is thus important to understand how fluids actually improve clinical problems and how one can predict fluid responsiveness. It is also important to understand potential limitations of fluid therapy.Currently there is a lot of attention being paid to the assessment of fluid responsiveness, but there is a lack of studies evaluating indications for fluid treatment and the potential harm from excess fluid use. This review emphasizes the physiological factors that determine the response to fluids, the limitations of these responses, and the predictors of fluid responsiveness. A key principle is that fluid resuscitation improves clinical indicators by increasing cardiac output, and if the volume infusion does not increase cardiac output there will be no benefit.Assessment of changes in cardiac output, either directly or indirectly, is a key component of managing fluid therapy. Avoiding harm with the use of fluids requires understanding what is physiologically possible.