There are two types of radiological weapon, “dirty bomb,” and nuclear weapon (atom bomb). A dirty bomb can be made from one or more commercially available radioactive isotopes and it can be detonated using a conventional explosive, whereas an atom bomb consists of fissionable element, and it requires complex procedures for detonation. Explosion of a radiological weapon can cause a few injuries to mass casualties, depending upon the type of radiological weapon, and can increase the chronic health risks among survivors. Bio-Shield refers to chemicals or biologics that can prevent or mitigate radiation injury when administered before and/or after irradiation. During past decades, several radiation preventive and mitigating agents been identified. They can be grouped into following categories: (a) chemicals not approved by the FDA, (b) drugs approved by the FDA for other conditions, (c) certain biologics approved by the FDA, and (d) antioxidants and herbs not requiring FDA approval. An effective bio-shield that can be recommended to humans must satisfy the following three criteria: (1) chemicals or biologics should prevent and/or mitigate radiation damage in the laboratory experiments when administered before and/or after irradiation; (2) they should show at least some evidence that they can prevent or mitigate radiation damage in humans; and (3) they at radiation preventive or radiation mitigating doses must be safe in human when administered on a short- or long-term basis. Published data show that most radiation preventing and mitigating chemicals, drugs or herbs satisfy only the first criterion of an effective bio-shield, whereas antioxidants satisfy all three.