The majority of patients starting dialysis already have signs of advanced atherosclerosis, and the risk factors for cardiovascular morbidity and mortality seen in patients with end-stage renal disease (ESRD) develop with the disease progression. Therefore, the predialysis period is the ideal time to start therapeutic interventions. Traditional risk factors alone may not adequately predict cardiovascular disease (CVD) outcome in patients with ESRD. Inflammation has been identified as playing a key role in atherosclerotic CVD. Pro-inflammatory cytokines are pivotal to the inflammation that is associated with malnutrition and atherosclerosis in ESRD. Malnutrition may worsen patient outcome by aggravating existing inflammation and heart failure, accelerating atherosclerosis and increasing susceptibility to infection. Atherosclerosis is itself a major risk factor for CVD mortality. Moreover, inflammation is associated with congestive heart failure. Strong associations between malnutrition, inflammation and atherosclerosis in this patient population suggest the presence of a syndrome we have called malnutrition, inflammation, and atherosclerosis (MIA), which is associated with an exceptionally high mortality rate.