The temporal relationship between the development of heart failure and activation of the neurohumoral systems involved in chronic heart failure (CHF) has not been precisely defined. When a compensatory mechanism switches to a deleterious contributing factor in the progression of the disease is unclear. This article addresses these issues through evaluating the contribution of various cardiovascular reflexes and cellular mechanisms to the sympathoexcitation in CHF. It also sheds light on some of the important central mechanisms that contribute to the increase in sympathetic nerve activity in CHF.