Even if trauma patients initially avoid death after trauma (due to massive blood volume loss, primary severe brain injury), they are still at risk for multiple organ failure. Thus, it is crucial to elucidate the underlying pathophysiological mechanisms of trauma/hemorrhagic shock and the immune response involved. As of now, many hemorrhagic shock/trauma studies have used various types of animal models. Despite a large number of results from these efforts, some authors have argued that animal model results are difficult to translate directly into the clinical scenario. This review summarizes the advantages and the disadvantages of using animal models in trauma/hemorrhagic shock studies and discusses the relevance of various animal studies to the clinical scenario.