Opioid-induced modulation of the immune system is a complex phenomenon involving opioid receptors, central and sympathetic neural pathways, catecholamine receptors, and other regulatory mechanisms. The precise neural pathways involved in centrally-mediated immune modulation are not currently defined. In addition, the physiological purpose for endogenous opioid modulation of the immune system is not well understood. Perhaps this modulation phenomenon represents an integral feedback loop within a much larger homeostatic control system. Indeed, the role of the HPA axis in immune regulation can not be discarded, and in fact, probably serves to balance immune function, in concert with multiple feedback systems, around some undiscovered parameter of efficiency. Perhaps the physiological role of endogenous opioid control is to act as a monitor poised to subvert chronic inflammatory processes and autoimmune disorders. Regardless of the evolutionary heritage of this and despite the overwhelming complexity of immune regulation, important work substantiating a bidirectional communication link between the brain and the immune system has created a foundation for further elucidation of the intricacies of immunoregulation.