Psychological stress has been linked empirically with dysregulation of facets of the human immune system, yet these effects are not the same in every situation or population. Recent research has made strides towards understanding risk factors for immune dysregulation as well as why these risks occur. This review discusses mechanisms and mediators underlying the stress-immune relation, the role of context in determining whether an immunologic responses to stress is adaptive versus maladaptive, and the stress-immune relation in populations including children exposed to early adversity, older adults, and individuals with clinical diagnoses. The reviewed work holds great promise for further elucidating the circumstances under which psychological stress has immunological consequences, and provides new directions for work in this field.