Previous studies have indicated that the vagus nerve can control inflammation, but the clinical applications of direct vagal stimulation are currently limited. Ulloa and colleagues now show that activation of the sciatic nerve through electroacupuncture, or by direct electrical stimulation, induces vagal activation of aromatic-L-amino acid decarboxylase in the adrenal gland, which leads to dopamine production in the adrenal medulla. In turn, dopamine inhibits lipopolysaccharide-induced inflammatory cytokine production, which controls systemic inflammation and rescues mice from polymicrobial peritonitis. Dopamine D1 receptor agonists mimic the anti-inflammatory potential of electroacupuncture and can rescue mice with adrenal insufficiency from peritonitis even when administered after the onset of sepsis. As there is no currently approved treatment for severe sepsis, these results hold promise for a clinical strategy combining electroacupuncture with dopaminergic agonists.