Current research is being directed toward the identification of markers of cardiac risk in hypertension, according to demographic, clinical, genetic, challenge-response and laboratory predictors. Much interest has centered around cationic transporters as laboratory markers, not only because they might make good predictors of cardiac risk, but also because of their potential for explaining the pathophysiology of that disorder. To date, there is no cationic transporter that clearly discriminates between subjects with low and with high cardiac risk, although the sodium-lithium (Na(+)-Li+) countertransport in red blood cells has come the closest. High rates of Na(+)-Li+ countertransport have been found to be associated not just with essential hypertension but more specifically with subgroups of patients suffering from essential hypertension who have a higher frequency of severe hypertension and increased risk of cardiac disease. Here, we examine different lines of clinical evidence suggesting that increased Na(+)-Li+ countertransport activity may identify patients with essential hypertension who are at an increased risk of cardiac disease because they also present other cardiac risk factors, namely hyperlipidemia and/or left ventricular hypertrophy. In addition, the pathophysiological basis for the association of hypertension and the above cardiac risk factors with increased Na(+)-Li+ countertransport are discussed.