The locus coeruleus (LC), as the primary source of norepinephrine (NE) in the brain, is central to modulating cognitive and behavioral processes. This review synthesizes recent findings to provide a comprehensive understanding of the LC-NE system, highlighting its molecular diversity, neurophysiological properties, and role in various brain functions. We discuss the heterogeneity of LC neurons, their differential responses to sensory stimuli, and the impact of NE on cognitive processes such as attention and memory. Furthermore, we explore the system's involvement in stress responses and pain modulation, as well as its developmental changes and susceptibility to stressors. By integrating molecular, electrophysiological, and theoretical modeling approaches, we shed light on the LC-NE system's complex role in the brain's adaptability and its potential relevance to neurological and psychiatric disorders.