The presence of ‘emerging contaminants’, i.e., chemicals yet without a regulatory status and poorly understood impact on human health and environment, in wastewater and aquatic environments is widely reported. No established technology, to date, can simultaneously and completely remove all these contaminants, even though some Advanced Oxidation Processes (AOPs,) have demonstrated capacity for some degradation of these compounds. High-energy, radiolytic processing of water matrices using various sources: electron beam (EB), ɣ-rays or non-thermal plasma (NTP) have shown excellent results in many applications, although these remain at the moment isolated examples and scarcely known. High-energy irradiation constitutes an additive-free process that uses short-lived, highly reactive radicals (both oxidating and reducing) generated by water radiolysis, which can instantaneously decompose organic pollutants. Several studies have demonstrated its effectiveness, as a stand-alone process or combined with others, in the rapid decomposition (up to complete mineralization) of organic compounds in pure and complex solutions, and in the removal or inactivation of microorganisms and parasites, without production of leftover residual compounds in solution. High-energy oxidation processes (a.k.a. Advanced Oxidation & Reduction Processes—AORPs) could have a primary role in future strategies addressing emerging contaminants.