Resilience represents an active adaption process in the face of adversity, trauma, tragedy, threats, or significant sources of stress. Investigations of neurobiological mechanisms of resilience opens an innovative direction for preclinical research and drug development for various stress-related disorders. The locus coeruleus norepinephrine system has been implicated in mediating stress susceptibility versus resilience. It has attracted increasing attention over the past decades with the revolution of modern neuroscience technologies. In this review article, we first briefly go over resilience-related concepts and introduce rodent paradigms for segregation of susceptibility and resilience, then highlight recent literature that identifies the neuronal and molecular substrates of active resilience in the locus coeruleus, and discuss possible future directions for resilience investigations.