The nervous system regulates immune function and inflammation. Experimental evidence shows an important role of the autonomic nervous system in the bidirectional communication between the brain and the immune system, underlying the ability of the brain to monitor immune status and control inflammation. Here we review the involvement of the autonomic nervous system in regulating inflammation, with a focus on the vagus nerve. The clinical implications of the recently discovered anti-inflammatory role of the efferent vagus nerve are also discussed.