Hypertension occurring during the course of dialysis is an increasingly recognized finding in ESRD patients treated with hemodialysis. In this review, we will describe the epidemiologic, observational, and experimental studies that have increased our understanding of the natural history, health consequences, pathophysiology, and potential prevention and treatment strategies for intradialytic hypertension. The observational evidence has led to the development of definitions of intradialytic hypertension that are validated in longitudinal cohort studies and are predictive of future health consequences from untreated intradialytic hypertension. The epidemiologic studies have demonstrated that intradialytic hypertension occurs much more commonly in ESRD patients treated with hemodialysis than previously appreciated. A number of lines of evidence support the view that intradialytic hypertension is an important independent risk factor for cardiovascular disease and for premature death. This body of evidence is discussed in the context Hill criteria for causation where intradialytic hypertension might be considered a harmful exposure causally linked to the development of cardiovascular disease. The majority of the Hill criteria are met supporting the view of a causal link. A number of laboratories using experimental and translational models have begun to elucidate the mechanisms that may mediate the intradialytic hypertension observed in a subset of hemodialysis patients. We shall review the emerging understanding of the epidemiology and pathophysiology that has led to the identification and validation of biomarkers of vascular dysfunction and/or dysregulation in patients exhibiting intradialytic hypertension. We shall review the evidence from short-term experimental trials evaluating potential interventions to treat or prevent this condition. To date, these studies have evaluated the effects of interventions on biomarkers of vascular dysfunction, on hormonal mediators of endothelial tone, and on intra- and interdialytic blood pressures in the short term. We shall review recommendations that can be justified by this new evidence and the limitations of this evidence in informing treatment. The lack of long-term RCT patient-centered outcome studies is particularly problematic when attempting to estimate the long-term benefits from treatment. Current recommendations which remain largely empiric include those for more robust surveillance for intradialytic hypertension and for its treatment, more focus on avoidance of volume overload and on avoidance of significant electrolyte imbalances during hemodialysis where these fluid and electrolyte imbalances may cause intradialytic hypertension, and more selectivity in medication choice for the pharmacologic management of hypertension in dialysis patients.