A great deal of interest has recently become focused on interactions between the nervous and the immune systems, including the potential for alterations in immune function to contribute to various psychiatric and neurologic disorders. Evidence suggests that cytokines may be involved in the development of depression. Immune-mediated mechanisms in the pathophysiology of some types of depression are reviewed from both clinical and animal studies and the difficulties inherent in studying the interplay of these two complex systems in the development of depression are described.