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Concern about health risks from exposure to non-ionizing radiation (NIR) commenced in the 1950s after tracking radars were first introduced during the Second World War. Soon after, research on possible biological effects of microwave radiation in the former Soviet Union and the U.S. led to public and worker exposure limits being much lower in Eastern European than in Western countries, mainly because of different protection philosophies. As public concern increased, national authorities began introducing legislation to limit NIR exposures from domestic microwave ovens and workplace devices such as visual display units. The International Radiation Protection Association (IRPA) was formed in 1966 to represent national radiation protection societies. To address NIR protection issues, IRPA established a Working Group in 1974, then a Study Group in 1975, and finally the International NIR Committee (INIRC) in 1977. INIRC’s publications quickly became accepted worldwide, and it was logical that it should become an independent commission. IRPA finally established the International Commission on Non-Ionizing Radiation Protection (ICNIRP), chartering its remit in 1992, and defining NIR as electromagnetic radiation (ultraviolet, visible, infrared), electromagnetic waves and fields, and infra- and ultrasound. ICNIRP’s guidelines have been incorporated into legislation or adopted as standards in many countries. While ICNIRP has been subjected to criticism and close scrutiny by the public, media, and activists, it has continued to issue well-received, independent, science-based protection advice. This paper summarizes events leading to the formation of ICNIRP, its key activities up to 2017, ICNIRP’s 25th anniversary year, and its future challenges.