Worldwide, one of the main causes of death among young adults is multiple trauma. In these pa-tients hemorrhagic shock represents the leading cause for worsening of the clinical status and for increased morbidity and mortality. This is due to a multifactorial complex involving cellular, bi-ological, and biophysical mechanisms. The most important mechanisms affecting clinical out-come are oxidative stress, the augmentation of pro-inflammatory status, immune deficiency, dis-ruptions in the coagulation cascade, imbalances in electrolyte and acid-base homeostasis. Poly-trauma patients in hemorrhagic shock need adequate fluid management to ensure hemodynamic stability that must consider not only the maintenance of adequate blood pressure, but also the ad-equate oxygenation of tissues for optimal cellular function. In the current clinical practice, fluid resuscitation in polytrauma patients uses a variety of widely studied pharmacological products, such as crystalloids, colloids, blood transfusions, and the infusion of other blood products. Alt-hough these products exist, an agreement was not reached on a standard administration protocol that could be generally applied for all patients. Moreover, numerous studies have reported a se-ries of adverse events related to fluid resuscitation and to the inadequate use of these products. This review aims at describing the impact the administration of all the solutions used in fluid re-suscitation might have on the cellular and pathophysiological mechanisms in the case of poly-trauma patients suffering from hemorrhagic shock.