This chapter reviews the experimental evidence that activation of the immune system, e.g., following infection or challenge (for example, with viruses), alters the metabolism of certain neurotransmitters in the brain, most notably serotonin, and the catecholamine, norepinephrine, and the amino acid tryptophan, as well as activating the hypothalamo-pituitary-adrenal (HPA) axis. There may be causal relationships between the noradrenergic activation and the HPA axis, and the neurochemical changes are implicated in the behavioral responses, in particular the sickness behaviors associated with injuries and infections. Nevertheless, there are many gaps in our knowledge, and we do not yet have a detailed understanding of the relationships between the immune activation and the brain responses.