Resistant hypertension is defined as a blood pressure above 140/90 mmHg despite adherence to a combination of at least three optimally dosed antihypertensive medications, one of which is a diuretic. Chronic kidney disease (CKD) is one of the more common patient comorbidities associated with resistant hypertension. Recommended low-salt diet and triple antihypertensive drug regimens that include a diuretic, should be complemented by the sequential addition of other antihypertensive drugs. CKD is associated with premature vascular ageing, characterized by accelerated arteriosclerosis or atherosclerosis and endothelial dysfunction. Vascular changes appear in the early stages of CKD, although they are most pronounced in advanced stages. Systolic hypertension is the most common form of hypertension in patients with CKD, and raised systolic BP is independently associated with risk of progression to chronic kidney disease. Rigid arterial walls attenuate baroreceptor control of efferent sympathetic activity and vagal activation. Reduced baroreflex sensitivity maintains high sympathetic activity directed to the heart, blood vessels, and kidney, which contributes to high BP. Patients with CKD also have an inadequate vasoconstrictor response to baroreceptor unloading, this contributes to frequent orthostatic hypotension and circulatory instability. Moreover, hypoxemia of renal tissue due to kidney damage activates the CNS via afferent nerves, which also contributes to high sympathetic activity. New therapeutic innovations for resistant hypertension, such as renal denervation and carotid barostimulation are under investigation especially in patients with advanced chronic kidney disease. One of the most common reasons for blood pressure resistance in CKD is volume overload with increased sympathetic activity also being a major contributor. We will focus on the epidemiology as well as pathophysiology and therapeutic approaches to managing resistant hypertension in CKD stages 3–5 not on dialysis).