Asymmetric dimethylarginine (ADMA) is a recently recognized endogenous inhibitor of nitric oxide production. Its role in cardiovascular disease is emerging, and ADMA appears to be an important causal factor in dysfunction of the vascular system. Several studies show that ADMA accumulates during renal failure, and ADMA has been identified as causing the cardiovascular complications accompanying renal failure. In addition to the kidney, we recently suggested an important role for the liver as an ADMA-eliminating organ. In a population of critically ill patients, hepatic failure was the most prominent determinant of ADMA concentration, and, notably, high ADMA concentration proved to be a strong and independent risk factor for intensive care unit mortality in these patients. We here summarize the role of both the kidney and the liver in the regulation of ADMA levels. In addition, the potential central role of ADMA as a causative factor in the development of multiple organ failure is discussed.