Activation of the sympathetic nervous system plays a critical role in the pathogenesis of hypertension. In particular, the central nervous system (CNS) organizes the sympathetic outflow and various inputs from the periphery. These include afferent neural inputs, circulating hormone, cellular factors, and inflammatory and immune responses. Also, within the brain, several factors affect and determine the central sympathetic outflow. Interestingly, these factors are activated particularly in the autonomic nuclei such as the paraventricular nucleus of the hypothalamus and rostral ventrolateral medulla of the brainstem. I will review what and how these factors are altered in various stages of hypertension from the results of basic studies using animal models of hypertension including our own and other investigators. I will address topics such as imbalance of nitric oxide and reactive oxygen species, activation of the brain renin-angiotensin pathway, and altered immunity including Toll-like receptor activation, regulatory T cell inhibition, and perivascular macrophages. In addition, activation of the mineral corticoid receptors in the CNS could be responsible for salt-sensitive hypertension. Finally, I will introduce some new aspects of neural mechanisms of hypertension in the recent progress in the field of research. These experimental studies regarding CNS mechanisms of hypertension can be translated to clinical practice and novel therapies.