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The existence of a network of interactions between the immune and nervous systems that influences host defenses and brain functions is now well-established. Here we discuss how immune and classical neuro/sensorial signals are processed in the brain and how neuro-endocrine immunoregulatory and behavioral responses are integrated. Considering the ability of brain cells to produce cytokines, originally described as immune cell products, we propose that the tripartite synapse plays a central role in the integration of neuro-endocrine-immune interactions. We also propose that the immune-neuro-endocrine responses that influence the course of transmissible and other diseases predisposing to infections can be relevant for evolution, either by restoring health or by mediating an active process of negative selection.