The communication between the central nervous system and the immune system occurs via a complex network of bidirectional signals linking the nervous, endocrine and immune systems. The field of psychoneuroimmunology (PNI) has provided new insights to help understand the pathophysiological processes that are linked to the immune system. Work in this field has established that psychological stress disrupts the functional interaction between the nervous and immune systems. Stress-induced immune dysregulation has been shown to be significant enough to result in health consequences, including reducing the immune response to vaccines, slowing wound healing, reactivating latent herpesviruses, such as Epstein-Barr virus (EBV), and enhancing the risk for more severe infectious disease. Chronic stress/depression can increase the peripheral production of proinflammatory cytokines, such as interleukin (IL)-6. High serum levels of IL-6 have been linked to risks for several conditions, such as cardiovascular disease, type 2 diabetes, mental health complications, and some cancers. This overview will discuss the evidence that psychological stress promotes immune dysfunction that negatively impacts human health.