Feedback activation of neurohormonal pathways in the setting of kidney or heart failure contributes to the development and progression of dysfunction in the other. Diabetes and its management independently activate these same pathogenic pathways, feeding into this vicious cycle and contributing to a poor prognosis. One of the most important of these neurohormonal pathways is the sympathetic nervous system (SNS). The activity of the SNS in increased in patients with chronic kidney disease, even in the absence of renal impairment or heart failure. There is a strong relationship between SNS overactivity and prognosis, and evidence that blockade of SNS reduces morbidity and mortality in patients with diabetes. However, modulation of SNS is underutilised as a strategy to protect both the diabetic kidney and the heart. This is partly because of the historically poor tolerability, adverse haemodynamic and metabolic effects, lack of selectivity of β-blockers and the lack of specificity of other interventions that might modify SNS activation. The advent of “vasodilating β-blockers” with better tolerability as well as more favourable effects on renal function and metabolic profiles opens the door for their more widespread utility in patients with diabetes. Radiofrequency renal sympathectomy and baroreflex activation technologies also offer exciting new ways to tackle the challenge of sympathetic overactivity.