Systemic inflammation characterizes several chronic diseases including uremia. Inflammation may contribute to morbidity and mortality by enhancing protein-calorie malnutrition, infectious complications, and atherosclerosis and cardiovascular disease. Although inflammation in renal disease can be caused, at least in part, by reduced renal clearance of proinflammatory mediators (tumor necrosis factor [TNF]-alpha, interleukin [IL]-6), several pathogenetic mechanisms are likely to contribute to direct activation of the inflammatory process under these conditions. These mechanisms include accumulation of advance glycoxidation end products, production of reactive oxygen species and oxidative damage, and chronic infection. Support for direct activation of systemic inflammation provides a strong rationale for use of anti-inflammatory treatments in uremia. The current article describes the association between uremia and inflammation, provides evidence for activation of inflammatory process, and provides potential therapeutic approaches.