Extensive efforts have been made to try to elucidate the pathophysiological mechanisms and the immunologic alterations associated with severe hemorrhage. A broad variety of experimental conditions have been established that enable investigators to study the effects of hypovolemic shock and to assess the potential benefits of a wide spectrum of treatment options. However, translating these experimental findings into clinically applicable therapy has been challenging, suggesting the need for a better understanding of the animal models being used. As certain advantages and disadvantages are associated with the different models of hemorrhage (such as controlled and uncontrolled hemorrhagic shock and combined trauma with hemorrhagic shock models, for this review, we have selected representative studies that reflect the current status of experimental shock research that looks at acute blood loss, and that may serve as a guide when considering which model or models to apply.