The incidence of disorders related to the control of energy homeostasis, such as hypertension, diabetes, obesity, and dyslipidemia, has dramatically increased worldwide in the last decades. The central nervous system (CNS) plays a critical role regulating the energy balance, therefore there has been increasing interest in understanding the mechanisms whereby the brain controls peripheral metabolism, in order to develop new potential therapies to treat those disorders. While the involvement of the CNS in development of hypertension, obesity, and diabetes has been thoroughly investigated, less is known about the specific role of the brain in the control of circulating lipids. Here we summarize the evidence linking CNS disorders with dyslipidemia, as well as the central mechanisms that directly influence plasma cholesterol.