Palladium-catalyzed site selective arylation reactions of both sp(2) and benzylic sp(3) sites on azine and diazine N-oxide substrates are described that occur in good to excellent yield and with complete selectivity for reaction at the desired position. These studies have uncovered the need to property control the metal to ligand ratio in sp(2) arylation and necessitated a complete reinvestigation of all reaction parameters for sp(3) arylation. From these studies, the choice of base emerged as a pivotal component for site selectivity, pointing to its intimate involvement in the mechanism of direct arylation. These site selective reactions have been validated in both divergent and sequential derivatizations of heterocyclic compounds represent an attractive alternative to other routes to this class of molecule.