This review discusses neurobiological and psychosocial factors associated with stress-induced depression and compares these factors with those believed to characterize stress resilience. Neurobiological factors that are discussed and contrasted include serotonin, the 5-HT1A receptor, polymorphisms of the 5-HT transporter gene, norepinephrine, alpha-2 adrenergic receptors, neuropeptide Y, polymorphisms of the alpha-2 adrenergic gene, dopamine, corticotropin-releasing hormone (CRH), dehydroepiandrosterone (DHEA), cortisol, and CRH receptors. These factors are described in the context of brain regions believed to be involved in stress, depression, and resilience to stress. Psychosocial factors associated with depression and/or stress resilience include positive emotions and optimism, humor, cognitive flexibility, cognitive explanatory style and reappraisal, acceptance, religion/spirituality, altruism, social support, role models, coping style, exercise, capacity to recover from negative events, and stress inoculation. The review concludes with potential psychological, social, spiritual, and neurobiological approaches to enhancing stress resilience, decreasing the likelihood of developing stress-induced depression/anxiety, and treating stress-induced psychopathology.