Whereas a well-regulated cytokine response that is rapidly triggered by the host’s innate immunity can serve to prevent and to counteract an infection, an excessive, unbalanced, prolonged immune response can seriously harm the body. Therefore, therapeutic strategies aimed at effectively suppressing the cytokine storm are under investigation. Nanomaterials have been exploited to adjust the immune response to an optimized level, and such proprieties might be explored to inhibit cytokine releases.99 Nanosystems can enhance the specificity/efficiency of immunosuppressant delivery to target immune cells, with consequent reductions in drug dose, drug distribution to nontarget tissues and organs, and possible side effects. In addition, specific nanotools can be designed to evade the immune system and to enhance the solubility of poorly soluble immunosuppressant agents; the potential of finely tuning their surface charge opens possibilities for encapsulation strategies and offers accommodation for a high drug load. All of these mechanisms may also occur simultaneously, enhancing the activity of immunosuppressive agents.