Folk wisdom has long suggested that stressful events take a toll on health. The field of psychoneuroimmunology (PNI) is now providing key mechanistic evidence about the ways in which stressors — and the negative emotions that they generate — can be translated into physiological changes. PNI researchers have used animal and human models to learn how the immune system communicates bidirectionally with the central nervous and endocrine systems and how these interactions impact on health.