The locus coeruleus-norepinephrine (LC-NE) system is involved in many brain functions and neurological disorders. In this review we discuss how LC-NE signaling affects the activity of cortical and subcortical sensory neurons, and how it influences perception-driven behaviors associated with mammalian somatosensory, visual, auditory, and olfactory systems. We summarize the consistent as well as seemingly inconsistent findings across brain areas and sensory modalities and propose a framework to understand these phenomena from the perspective of adrenergic receptor expression, dose-dependent physiology and excitation-inhibition balance. We also discuss potential future research directions in this field.