PART 1: A computational analysis of the mechanism of Ir-catalyzed enantioselective hydrogenations of pyridinium salts is outlined. Using density functional theory (DFT) methods, energetics of the proposed mechanism was determined, focusing on the determination of the enantioselectivity determining step. Analysis suggested an unusual enantioselectivity mechanism. The absolute stereochemistry of the product is likely determined during protonation of the enamine, early in the reaction. The stereoinduction mechanism was applied to various substituted pyridinium salts and was also powerful in predicting the stereochemical outcome of the related benzodioxIne reduction. PART 2: A computational analysis of the reactivity of organonickel species, intermediates in photocatalyzed cross-coupling reactions, is presented. The competition between radical dissociation and reductive elimination reactions was investigated, with a focus on control via ligand modifications. A detailed analysis of the isomeric Ni(III) complexes and the potential equilibration routes between them allowed the identification of the most likely reaction pathways. Using these pathways, the reactivity of complexes incorporating two classes of ligands was evaluated. A statistical relationship was found between parameters of complexes and their relative reactivity in these transformations. The results of this study will be used to construct further robust and predictive statistical reactivity models. PART 3: Reduction of pyridinium salts to corresponding radicals and subsequent dissociation provides a new method for efficient C-N bond activation. I computationally analyze the reactivity of substituted pyridinium salts and pyridinium radicals in reduction and radical dissociation, respectively. Using DFT calculations, I determined the effect that substitution of the pyridine moiety has on the reactivity of corresponding species. The theoretical analysis culminated in an experimentally validated prediction of the reactivity trends. General design principles for pyridine modifications are formulated. PART 4: In this chapter, I discuss some of the computational work performed in Kozlowski’s laboratory on the chemoselective and regioselective oxidative additions of palladium catalysts across carbon-halogen bonds. This computational study uncovered an unusual oxidative addition mechanism, which is likely responsible for determining the selectivity of the reaction catalyzed by the Pd-DPPP complex. This newly identified mechanism is related to a conventional heterocyclic SNAr mechanism and may operate in multiple heterocyclic systems in cross-coupling.