A hallmark of cardiovascular diseases such as hypertension and heart failure is an elevation in sympathetic nerve activity (SNA), especially to the heart and kidneys. In the case of heart failure, levels of cardiac and renal norepinephrine spillover have been reported to be as much as 50 times above normal (Esler & Kay, 1998). Understanding the significance of the elevation in renal SNA would seem essential given sympathetic activation to the kidney is associated with poor prognosis (Petersson et al. 2005). Elevations in renal SNA result in renal vasoconstriction, increased renal sodium retention and increased renin release, and consequently elevated angiotensin II and aldosterone levels (DiBona & Kopp, 1997). Sensory information from baroreceptors, chemoreceptors and osmoreceptors all modulate SNA. In our laboratory we have employed the use of telemetry to continuously monitor arterial pressure and renal sympathetic nerve activity in conscious, freely moving animals. We have demonstrated that, in the case of hypertension, the elevation in renal SNA is dependent on circulating levels of angiotensin II, salt intake and a function of time (Guild et al, 2012). Removing the renal sympathetic nerves shifts the renal pressure-natriuresis curve to the left, promoting urinary sodium excretion and lowering of blood pressure. As a consequence renal nerve ablation, using radio frequency energy to denervate the renal nerves, is rapidly gaining popularity as a potential treatment for a plethora of cardiovascular diseases. While in general it would seem that decreasing renal SNA is the key to the clinical management of cardiovascular disease, it is clear that this approach is simplistic. There are situations where hypertension is not necessarily accompanied by an increase in renal SNA. In our own animal models we have observed a decrease in renal SNA in response to a pressor dose of angiotensin II. This decrease in SNA is mediated by the arterial baroreceptors and sustained for at least 7 days (Barrett et al, 2005) illustrating the potential importance in establishing whether or not an elevation in renal SNA does contribute to the hypertension prior to considering renal denervation. By continuously recording renal SNA in rats following coronary ligation to induced heart failure we have observed a gradual increase in renal SNA, with nerve activity doubling within 14 days of the ligation. The exact cause of this increase in SNA remains contentious with blunted baroreceptor reflex, sensitization of the chemoreflexes, increased levels of circulating angiotensin II, oxidative stress and reduced levels of nitric oxide among the potential contributing factors. To further complicate matters in chloralose-urethane anaesthetised rats we have demonstrated that the change in renal sympathetic nerve activity immediately following coronary ligation is sex dependent, with greater increases in male versus female rats. The sex differences in the response to coronary ligation can, at least in part, be explained by the sex-differences observed in the arterial baroreflex control of renal SNA. The benefit of renal nerve denervation in heart failure remains unclear, but there is at least preliminary evidence to suggest renal nerve denervation can improve fluid balance and cardiac function in heart failure. Proof of concept clinical studies suggest that arterial pressure in patients with heart failure is maintained post renal nerve ablation (Davies et al. 2013), although whether such patients can then cope with additional stressors such as sepsis or haemorrhage remains to be determined.Clinical and experimental evidence generally suggests reducing renal sympathetic nerve activity should be a major aim in the clinical management of hypertension and heart failure. However, understanding the exact nature of the changes in renal SNA that occurring during the progression of the disease is essential if treatment is to be effective.