This article summarizes the endocrine and immune changes induced by an experimental model for social stress characterized by repeated defeat. Data indicate that mice facing a social stressor may use different behavioral coping responses based on the environmental conditions and previous experiences. Although chronic stressors generally suppress immune function and increase a host’s susceptibility to disease, this may not be always true in all cases. For example, under conditions in which individuals face the chance of being injured repeatedly, it may be an adaptive advantage to maintain or even enhance an immune response. The development of glucocorticoid resistance after social disruption may be such a mechanism, allowing animals to heal injuries and clear invading microbes in the presence of the anti-inflammatory stress hormones.