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The noradrenergic and cholinergic modulation of functionally distinct regions of the brain has become one of the primary organizational principles behind understanding the contribution of each system to the diversity of neural computation in the central nervous system. Decades of work has shown that a diverse family of receptors, stratified across different brain regions, and circuit-specific afferent and efferent projections play a critical role in helping such widespread neuromodulatory systems obtain substantial heterogeneity in neural information processing. This review briefly discusses the anatomical layout of both the noradrenergic and cholinergic systems, as well as the types and distributions of relevant receptors for each system. Previous work characterizing the direct and indirect interaction between these two systems is discussed, especially in the context of higher order cognitive functions such as attention, learning, and the decision-making process. Though a substantial amount of work has been done to characterize the role of each neuromodulator, a cohesive understanding of the region-specific cooperation of these two systems is not yet fully realized. For the field to progress, new experiments will need to be conducted that capitalize on the modular subdivisions of the brain and systematically explore the role of norepinephrine and acetylcholine in each of these subunits and across the full range of receptors expressed in different cell types in these regions.