The effects of neutron radiation on nickel-based alloys in thermal reactors are defying predictions that were made based upon accelerated testing in fast reactors. As nickel-based alloy components face significant doses in aging thermal reactors and their role in Gen-IV reactor designs becomes prominent, the literature on the effects of radiation on such alloys must be reviewed to enable better structural integrity assessments for relevant components and optimise alloys with respect to irradiation embrittlement resistance. This paper reviews the available data on the effects of radiation, notably neutron radiation, on nickel-based alloys and discusses the possible mitigation strategies and design opportunities for radiation embrittlement-resistant alloys based on recent developments in alloy computational design. This review was submitted as part of the 2016 Materials Literature Review Prize of the Institute of Materials, Minerals and Mining run by the Editorial Board of MST. Sponsorship of the prize by TWI Ltd is gratefully acknowledged.