Hypertension is a very common finding in hemodialysis patients and one of the most important risk factors for cardiovascular disease, the leading cause of morbidity and mortality in dialysis. The discontinuous nature of hemodialysis gives blood pressure a unique profile and makes the pathogenesis of hypertension complex in this population. Water and sodium retention play a pivotal role; increased activity of vasoconstrictive systems and impaired vasodilatation, hyperparathyroidism, erythropoietin, salt intake and dialysis prescription have also a role in blood pressure regulation. Aggressive treatment of hypertension must be the default approach in hemodialysis patients. The primary goal should be a strict control of body sodium content and extracellular volume by performing an optimal renal replacement therapy. If this approach proves unsuccessful, patients may benefit from antihypertensive medications. All classes of antihypertensive drugs can be used, with the sole exception of diuretics (although selected patients may advantage from furosemide therapy). Drug use, dosing, and frequency are dictated by pharmacokinetic considerations and peculiar dose adjustments must be adopted in this setting. The presence of end-stage renal disease also modifies the pharmacologic response in some cases, for example, the greater occurrence of orthostatic hypotension with alpha-blockers in a volume-depleted patient. The purpose of this review is to show the pathophysiological mechanisms, evaluate the on-going discussion about measurement techniques and recommended targets, and discuss the most appropriate management of hemodialysis-associated hypertension.