The main challenge in creating functional artificial peroxidases is the transient generation of high-valent intermediates and channeling their reactivity towards selective oxidation. These are implicated in a variety of hemoprotein-catalyzed oxidation processes. Native HRP regulates these intermediates to direct them toward productive oxidative reactivity. The 'Poulos-Kraut' mechanism has shed light on how HRP achieves this control by capitalizing on second-sphere interactions to stabilize key intermediates, thus enabling selective oxidation while minimizing side-reactions and oxidative degradation of the protein scaffold. Accordingly, it is widely accepted that stabilization of the high-valent intermediates is critical in enhancing the efficiency of functional peroxidase mimics.