Stress has profound effects on vertebrate immunity, but most studies have considered stress-immune interactions in terms of wild animals enduring demanding, but predictable activities (e.g., immune alterations during breeding). A growing biomedical literature, however, indicates that stress may not be obligatorily immunosuppressive; in response to transient, unpredictable stressors, immune activity can be enhanced, especially in body areas requiring immune protection. Also, immune sensitivity to stressors is not fixed throughout life; oftentimes, glucocorticoid (CC) insensitivity can be induced. Further CC sensitivity can be programmed early in life; greater exposure to stressors prior to maturity heightens CC effects on immunity in adulthood. In the present paper, I review the cellular and molecular mechanisms that link stress responses to immune adjustments over short time scales in domesticated species then I attempt to place stress-immune interactions in a naturalistic, organismal context. When, how and why stressors affect immunity in wild animals remains practically unstudied. (C) 2009 Elsevier Inc. All rights reserved.