Dimethylated L-arginine analogs have been attracting the attention of both basic researchers and clinicians for 15 years since 1992 when Vallance et al. were first to observe several fold elevations of asymmetric and symmetric dimethyl-L-arginine levels (ADMA and SDMA, respectively) in plasma of hemodialyzed patients. ADMA – in contrast to SDMA – competes with L-arginine at the level of NO synthase with consequent inhibition of NO generation. Later studies have revealed excessive ADMA accumulation in the presence of atherosclerotic risk factors and endothelial dysfunction even in patients free of clinical evidence of atherosclerosis. Moreover, ADMA concentrations were elevated also in proportion to the severity of carotid, coronary and peripheral atherosclerosis. Additionally, in vitro studies have shown the ability of proinflammatory cytokines and oxidized low-density lipoproteins to increase liberation of ADMA by cultured endothelial cells. This evidence has provoked a hypothesis that ADMA may accelerate atherogenesis by inhibition of endothelial NO synthase. Indeed, ADMA concentration proved to be an independent adverse outcome predictor in end-stage renal disease and in coronary artery disease. On the other hand, it remains an intriguing issue how ADMA is able to exert any biological effects in the presence of saturating L-arginine concentrations which are well above the Michaelis-Menten constant of endothelial NO synthase for Larginine. Recent years have brought novel fascinating findings in the field of research on dimethylated L-arginine analogs. First, ADMA has been shown to accelerate replicative senescence of endothelial cells via inhibition of the activity of telomerase, an enzyme counteracting telomere attrition, a molecular “clock”. Second, ADMA impairs the mobilization and activity of bone marrow-derived endothelial progenitor cells that participate in continuous endothelial renewal and neovascularization of ischemic tissues. Third, SDMA – previously considered an inactive stereoisomer of ADMA – has been demonstrated to inhibit NO synthesis via competition with L-arginine uptake by endothelial cells. As SDMA rises in earlier stages of renal dysfunction than ADMA, it may contribute to excessive cardiovascular morbidity in chronic kidney disease.