Paracetamol (PCT) or acetaminophen is a widely prescribed drug to treat fever and mild to moderate pain. The PCT uptake by animals and humans is not complete, being excreted through their urine to contaminate the aquatic/natural environments. Trace amounts of this drug have been found in sewage sludge, hospital wastewaters, wastewater plant treatments, surface waters, and even drinking water. PCT denatures proteins and oxidize lipids in cells with damage of their genetic code. Its toxicity over macrophytes, protozoan, algae, bacteria, and fishes has been reported. Ozonation methods have been proposed as efficient treatments to solve this pollution. This comprehensive and critical review is focused on the application of ozonation processes to remove PCT polluted water from different sources, like natural waters, synthetic waters, and real wastewaters. The fundamentals, operating variables, and best results by direct ozonation and hybrid catalytic ozonation are described, with attention to produced reactive oxygen species and their oxidative action. Single ozonation, catalytic modification of materials, and hybrid non-catalytic processes are detailed as direct ozonation methods. Ozonation with metal-based catalysts and photolytic and photocatalytic ozonation as hybrid catalytic methods are analyzed. Sequential non-biological and biological treatments with ozone and ozonation for wastewater remediation in treatment plants are described. Reaction sequences proposed for PCT mineralization are finally discussed, showing the initial formation of hydroquinone and 2-hydroxy-4-(N-acetyl)-aminophenol and their consecutive evolution to ultimate carboxylic acids like oxalic and oxamic. The ability of the methods to destroy these acids and their iron- and/or copper-complexes explains their mineralization performance.