Nonheme iron dioxygenases catalyze a range of vital reactions for human health, including the biosynthesis of hydroxyproline, the catabolism of cysteine as well as DNA repair mechanisms.[1] There are many facets to the catalytic reaction mechanism of these enzymes that are still elusive, which is partially due to their high reactivity but also as a result of multiple spin states interfering into the reaction mechanism. In this presentation, I will give an overview of recent computational studies of our group on the mechanism and function of a nonheme iron hydroxylase (prolyl-4-hydroxylase)[2] and a nonheme iron halogenase (hectochlorin biosynthesis protein).[3] In both enzymes the oxidant triggers a regio- and stereospecific reaction mechanism and the calculations were focused on understanding the reactivity patterns and particularly the importance of the secondary structure of the protein to guide the regio- and stereospecific product formation through proper substrate positioning but also through electrostatic interactions.