The brain and immune system form a bidirectional communication network in which the immune system operates as a diffuse sense organ, informing the brain about events in the body. This allows the activation of immune cells to produce physiological, behavioral, affective, and cognitive changes that are collectively called sickness, which function to promote recuperation. Fight-flight evolved later and coopted this immune-brain circuitry both because many of the needs of fight-flight were met by this circuitry and this cooptation allowed the immune system to respond to potential injury in anticipatory fashion. Many sequelae of exposure to stressors can be understood from this view and can take on the role of adaptive responses rather than pathological manifestations. Finally, it is argued that activation of immune-brain pathways is important for understanding diverse phenomena related to stress such as depression and suppression of specific immunity.