The sympathetic nervous system plays an important role in the regulation of arterial pressure, and increased sympathetic nervous system activity has been implicated as a primary precursor of hypertension in both humans and animal models of the disease. To date, the mechanism that potentiates the increase in sympathetic nervous system activity has not been fully elucidated. Imbalances in several neurotransmitters and neuromodulators are present during the development of hypertension, and these directly and indirectly contribute to increased release of noradrenaline onto the postsynaptic targets of the sympathetic nerves. In sodium chloride-sensitive hypertensive subjects, dietary sodium chloride increases sympathetic nervous system activity both directly and indirectly. Bidirectional interactions among the immune system and the sympathetic nervous system also appear to play a role in the development of hypertension. Finally, recent studies suggest that insulin-glucose excess and nitric oxide deficiency may increase the sympathetic nervous system's contribution to some forms of hypertension.