Lytic polysaccharide monooxygenases (LPMOs) are unique mono-copper enzymes that exhibit a broad range of functions: They boost the degradation of recalcitrant and insoluble polysaccharides, making them essential components of industrial enzyme cocktails used in sustainable biofuel production. Additionally, LPMOs have been shown to contribute to plant pathogen virulence and potentially also to human diseases. Furthermore, a recent study reported LPMO activity on poly(3-hydroxybutyrate) -a biodegradable plastic polymer -enabling the leverage of the LPMO reactivity in degradation of microplastic pollutants. LPMOs are grouped into eight different families of carbohydrate-active enzymes with auxiliary activities (AA9-AA11 and AA13-AA17). The eight families differ substantially in their substrate specificy, active-site architecture and also their reactivity. The natural substrates of LPMOs are different polysaccharides such as cellulose, chitin, starch and pectin. Strikingly, the only structural motif that is strictly conserved across all eight families is the active-site histidine brace, which consists of two histidine residues that coordinate a single copper atom. In most LPMOs, the histidine brace is located on a flat and solvent-exposed surface that enables the enzymes to be active on their polysaccharide substrates. LPMOs boost polysaccharide degradation by catalyzing the oxidative cleavage of the different polysaccharides, by inserting an oxygen atom into the C-H bonds of the glycosidic linkages. This oxygen atom is provided by either O 2 or H 2 O 2 . Steadily growing experimental and computational evidence suggests that H 2 O 2 is the preferred (and possibly only ) co-substrate, making LP-MOs the first copper enzymes known to carry out a peroxygenase reaction. A complicating factor for the elucidation of the LPMO mechanism has been that LPMOs, in absence of polysaccharide substrate, can generate H 2 O 2 from O 2 (oxidase reactivity). Only a reductant must be present as any LPMO activity requires an initial "priming" reduction of the active-site Cu(II) to Cu(I). The oxidase activity is commonly measured in experimental studies, showing that multiple LPMO families with different substrate specificity generate H 2 O 2 and that the rates of H 2 O 2 production can differ considerably between LPMO families but even within the same family. Under typical experimental conditions where no exogenous H 2 O 2 is added, substrate oxidation may rely on this in situ generation of H 2 O 2 , and it is thus possible that the H 2 O 2 production may be rate determining. However, excess H 2 O 2 can lead to oxidative damage and inactivation of LP-MOs, especially when the substrate is absent or only present in low concentrations. Therefore, understanding the detailed mechanism of H 2 O 2 generation is crucial for controlling LPMO activity and avoiding enzyme inactivation.