That the heart enlarges in patients with heart disease has long been known, but the structural details of this enlargement and the mechanism and rationale of this enlargement have only become apparent in recent years. As noted by Marc Pfeffer in his historical perspective, concepts were confused until quite recently. A focus on left ventricular function satisfied clinical physiologists that the enlargement was a manifestation of the heart calling upon its Frank Starling mechanism to support output from a dysfunctional ventricle. Rather than adverse, this presumed dilation was interpreted as an appropriate compensation for an increased workload or a deficiency in contractile function. The hypertrophy that accompanied this dilation was also viewed as compensatory, reflecting what was thought to be a pressure or volume overload that was being appropriately compensated for by an increase in mass. Although hypertrophy was recognized as a manifestation of ischemic heart disease, the concept of a structural remodeling process independent of pressure or volume load or contractile dysfunction was not entertained until more recently. The first four papers in this symposium provide remarkable insight into what we have learned in recent years about the structural remodeling process. Pfeffer reviews the work of his late wife, Dr. Janice Pfeffer, who began with models of hypertension that served as the classic etiology of both experimental and clinical hypertrophy. The idea that increased wall stress could induce hypertrophy as a result of volume increase without pressure increase was certainly an intuitive expansion of the well-known La Place relationship. Observations in the infarct model, however, began to challenge the simple hypothesis that load was the sole determinant of hypertrophy. And the evidence, largely from experimental and clinical intervention studies, that hormonal factors may be directly responsible for these structural changes opened the field to the exciting physiologic, cellular, and molecular studies that characterize today’s research and the focus of the rest of this symposium. Recognition that structural remodeling may develop as an early manifestation of heart disease in the absence of usual signs and symptoms has emphasized the challenge of early detection. Indeed, demonstration in the Studies of Left Ventricular Dysfunction (SOLVD) Prevention Trial of the effectiveness of intervention in such patients with an angiotensin-converting enzyme inhibitor has provided the stimulus for such early recognition and treatment. Rodeheffer provides an overview of studies that have explored populations to determine the prevalence of ventricular dysfunction. He addresses both the typical syndrome with a dilated left ventricle and a low ejection fraction and the syndrome of diastolic dysfunction that may present as symptomatic heart failure. Important as these studies are, they are plagued by the vagaries of the definitions of abnormal cardiac structure and function. Echocardiography is notorious for observer variability and measurement inconsistency. Thus both the ejection fraction selected as the lower level of normal and the precision of the methodology will influence the frequency of “abnormals” in an asymptomatic population. Quantitating diastolic dysfunction is even more problematic. As Rodeheffer points out, the availability of point-of-care b-type natriuretic peptide assays may help to separate “normal variant” from “disease.” But the gold standard, as he suggests, will be the follow-up of individuals who are identified as abnormal. Only then will the specificity and sensitivity of our screening attempts be quantitated. Carabello provides a thoughtful updating of the traditional views about concentric (pressure overload) and eccentric (volume overload) ventricular remodeling. He emphasizes the individual variability in response that may be critical to outcome. Furthermore, he addresses the importance of understanding that hypertrophy is a balance From the Cardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota Reprint requests: Jay N. Cohn, MD, Cardiovascular Division, Mayo Mail Code 508, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, MN 55455 Copyright 2002, Elsevier Science (USA). All rights reserved. 1071-9164/02/0806-0017$35.00/0 doi:10.1054/jcaf.2002.129265 Journal of Cardiac Failure Vol. 8 No. 6 Suppl. 2002