Acute radiation syndrome represents the clinical response of radiation-sensitive key tissues (i.e., hematopoietic, gastrointestinal and neurovascular) following exposure to high doses of ionizing radiation. In this context, the hematopoietic syndrome remains the first therapeutic challenge. Today, identifying new drugs and developing new strategies to cope with acute radiation syndrome remain a priority, especially to prevent/cure the radiation-induced multiple organ dysfunction syndrome then failure. Cytokine, non-cytokine drugs, and cell/gene therapy represent a pattern of sophisticated approaches developed by this group and others to achieve this goal.