Accessible online at: www.karger.com/journals/nef Prof. Claudio Ronco is Visiting Professor of Medicine at Albert Einstein College of Medicine and Director of the Renal Research Laboratory, Division of Nephrology and Hypertension at Beth Israel Medical Center and Renal Research Institute, New York. In the last two decades, a growing body of evidence has accumulated suggesting that oxidative stress may be one of the important complications occurring in hemodialysis (HD). This problem may not have immediate clinical effects, but it may represent a long-term complication derived from the repetitive effects of blood-membrane interaction [1–3]. Advanced experimental and clinical investigation regarding the mechanisms of oxidative stress during HD have elucidated the role of blood cell activation, and particularly polymorphonuclear (PMN) leukocytes. However, the multifactorial nature of this process [4] might include other factors peculiar to chronic HD, such as the absence of a complete correction of the uremic toxicity, malnutrition and the progressive worsening of the clinical condition due to aging and comorbidity. Altogether these factors trigger oxidative stress by establishing a steadily abnormal production of prooxidant stimuli coupled with a defective or insufficient antioxidant protection [1–3]. Phagocyte activation can generate reactive oxygen species (ROS) during the so-called respiratory burst [4]. These molecules exert a physiological role participating in the killing of bacterial and tumor cells [5] and in cell signaling [6]. From another perspective however, if chemical reactivity of these molecules is not properly controlled and limited, they may become extremely dangerous leading to the oxidative modification of biologically relevant molecules such as lipids, proteins and nucleic acids [2, 4]. Ultimately, a series of acute and chronic responses (damage, repair and adaptation) may arise in tissues and organs, the physiopathological relevance of which has been extensively documented [4, 7]. Oxidative stress has been proposed to play a role in many states often associated with end-stage renal disease, including cardiovascular and infectious diseases, cancer, diabetes, disorders of peripheral and central nervous system, anemia and accelerated aging [1–4]. Even if a direct cause-effect relationship between HD and oxidative stress-related disease states has not been definitively demonstrated, the repeated activation of the immune cells during the extracorporeal treatment may be a key aspect implying the onset of long-term side effects and an increased morbidity and mortality in hemodialysis patients. Exploring in detail the possible consequences of an increased oxidative stress in HD patients, we may come up with a list of disorders that include: (1) Lipoprotein modification: this is one of the major events associated with oxidative stress and, together with the ROS damage to endothelial cells, it is considered one of the earliest key events in the formation of atheromatose plaque [8].