The recent COVID-19 pandemic has brought attention to cytokines and the phenomenon of cytokine storm into mainstream discussions. In this disease specifically, a cytokine storm overwhelming immune response contributes to the pathophysiology and mortality of the COVID-19 infection. Analogous perturbed immune reactions are experienced in polytrauma patients, compromising local tissue healing while threatening multiple organ systems. The expanding field of osteoimmunology should contribute to the orthopaedic community's understanding of how the immune system response, whether normal or pathologic, affects the whole body outcome of our patients.