Naturally occurring high valent Heme and nonheme transition metal-dependent metalloenzymesMetalloenzymes and their biomimetic modelsBiomimetic models are highly reactive and selective towards various oxidative and reductive transformations. Understanding the mechanism of catalytic reactionsCatalytic reactivity of these enzymes and their biomimetic modelsBiomimetic models is extremely important for designing novel catalysts. However, the majority of the reported catalysts possess unpaired electrons, and the open-shell nature of the catalyst, with often close-lying spin-states, is challenging for the theoretical methods to model and comprehend the associated mechanistic aspects. In this regard, computational tools have played a pivotal role in underpinning the mechanism, and several important concepts, such as two-state/multi-state reactivity and exchange-enhanced reactivity, have emerged over the years to comprehend such complex mechanistic aspects. Additionally, the protein environment and various external factors, such as local electric fields generated by charged species, play crucial roles in completing the understanding of the underlying mechanistic aspects. In this chapter, we have summarized a range of theoretical efforts to provide a comprehensive overview of the reactivity of prominent, naturally occurring transition metal-dependent metalloenzymesMetalloenzymes and their biomimetic modelsBiomimetic models. These studies delve into various properties, such as the nature of the active site structure, spectroscopic evidence offering insights into the nature of the oxidant, the kinetics of various transformations that are catalyzed, and the dynamics of the protein and its role in facilitating reactivity. Additionally, we discuss relevant biomimetic modelsBiomimetic models developed to foster industrial applications of such catalytic processes.