The U.S. Department of Energy is sponsoring the Generation IV Initiative in the United States for the purposes of developing future-generation nuclear energy systems. Six systems have been selected for Generation IV consideration: gas-cooled fast reactor, lead-cooled fast reactor, molten salt-cooled reactor, sodium-cooled fast reactor, supercritical water-cooled reactor, and very high temperature reactor. Critical to the development of Generation IV concepts is successful development and deployment of materials that operate successfully in the aggressive operating environments envisioned in the Generation IV concepts. This paper summarizes the Generation IV operating environments and describes materials challenges and potential solutions, including crosscutting solutions applicable to multiple Generation IV concepts.