BACKGROUND: In the space environment, the traditional radioprotective principles of time, distance, and shielding become difficult to implement. Additionally, the complex radiation environment inherent in space, the chronic exposure timeframe, and the presence of numerous confounding variables complicate the process of creating appropriate risk models for astronaut exposure. Pharmaceutical options hold tremendous promise to attenuate acute and late effects of radiation exposure in the astronaut population. Pharmaceuticals currently approved for other indications may also offer radiation protection, modulation, or mitigation properties along with a well-established safety profile. Currently there are only three agents which have been clinically approved to be employed for radiation exposure, and these only for very narrow indications. This review identifies a number of agents currently approved by the U.S. Food and Drug Administration (FDA) which could warrant further investigation for use in astronauts. Specifically, we examine preclinical and clinical evidence for statins, nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), metformin, calcium channel blockers, β adrenergic receptor blockers, fingolimod, N-acetylcysteine, and pentoxifylline as potential radiation countermeasures.McLaughlin MF, Donoviel DB, Jones JA. Novel indications for commonly used medications as radiation protectants in spaceflight. Aerosp Med Hum Perform. 2017; 88(7):665–676.