An update is given of the circulating markers and mediators of cardiovascular dysfunction in acute illness. Some of these circulating markers reflect mediator action on the peripheral vasculature, such as endothelium-derived endothelin and nitrite/nitritate, the stable end products of nitric oxide. Other markers mainly reflect actions on the heart, such as the natriuretic peptide family, released from the heart upon dilatation, serving as a marker of congestive heart failure and potentially having negative inotropic effects. Indeed, some factors may be both markers as well as mediators of cardiovascular dysfunction of the acutely ill and bear prognostic significance. Assessing circulating levels may help refine clinical judgment of the cardiovascular derangements encountered at the bedside, together with clinical signs and hemodynamic variables. For instance, assessing natriuretic peptides in patients with pulmonary edema of unclear origin may help to diagnose congestive heart failure and cardiogenic pulmonary edema, when the pulmonary capillary wedge pressure is not measured or inconclusive. Future aligning of hemodynamic abnormalities with patterns of circulating cardiovascular markers/mediators may help to stratify patients for inclusion in studies to assess the causes, response to therapy and prognosis of cardiovascular derangements in the acutely ill.