Transfusion support of patients with hemorrhagic shock has changed over time with the development of storage and processing methods. Transfusion medicine developed during World War I with the use of whole blood, and now in the developed world, component therapy predominates. In contrast, there is still clinical use of fresh whole blood (FWB) in the developing world, in a minority of children's hospitals, and in combat settings. Although there is a rationale for the use of FWB in massively bleeding patients compared with the use of individual components, it has rarely been analyzed in prospective randomized clinical trials. Recent retrospective studies in adult trauma and mixed critically ill patients have revived this decades-old controversial question of the value of FWB for patients with severe shock and coagulopathy or those at risk. The risks of FWB use have also been highlighted recently, which has caused some to focus on reducing these risks with alternative processing and storage methods. It is important to recognize that current processing and storage methods for components have also not been adequately explored to determine whether they affect clinical outcomes. In this article, we review potential benefits and risks of FWB use for patients with hemorrhagic shock from any cause, and how current and future processing and storage methods may affect efficacy and safety of FWB in this population. We intend this review to stimulate hypothesis generation and clinical investigation in determining when FWB may be indicated and how to optimally process and store FWB to maximize its risk-benefit ratio.