Klinefelter’s syndrome (KS) is the most common sex-chromosome male disorder, characterized by one or more extra X chromosomes. It is associated with a significant increase of cardiovascular mortality and morbidity. This review examines cardiovascular (CV) abnormalities known in KS until now. KS is associated with both functional and structural CV alterations, particularly KS patients show a wide range of CV abnormalities, specifically LV diastolic dysfunction, impaired exercise performance, Chronotropic Incompetence (CI), and increased carotid intima-media thickness (IMT). Regarding diastolic function, they display an increased Isovolumetric Relaxation Time (IVRT) but no prolongation of Mitral deceleration Time (MdT). This condition indicates the presence of a mild diastolic dysfunction. KS patients also have an exercise intolerance, that depends on reduced stroke volume during exercise, caused by the limited increase in the LV end-diastolic volume despite normal ejection fraction and the increased LV filling pressure and left atrial pressure during exercise. Patients with KS also display a significant increase of carotid IMT, a surrogate marker of atherosclerotic disease. This alteration represents a subclinical marker of early atherosclerosis and is the most important risk factor of new or recurrent stroke and myocardial infarction. Testosterone replacement therapy does not normalize the impaired cardiovascular parameters. This wide range of CV abnormalities represents the pathophysiological underpinnings for the raised mortality observed in KS.