The application of Fenton-based advanced oxidation processes (AOPs), such as photo-Fenton or electro-Fenton for wastewater treatment have been extensively studied in recent decades due to its high efficiency for the decomposition of persistent organic pollutants. Usually Fenton-based AOPs are used for the degradation of targeted pollutant or group of pollutants, which often leads to the formation of toxic by-products possessing a potential environmental risk. In this work, we have collected and reviewed recent findings regarding the feasibility of Fenton-based AOPs (photo-Fenton, UVC/H₂O₂, electro-Fenton and galvanic Fenton) for the detoxification of real municipal and industrial wastewaters. More specifically, operational conditions, relevance and suitability of different bioassays for the toxicity assessment of various wastewater types, cost estimation, all of which compose current challenges for the application of these AOPs for real wastewater detoxification are discussed.