A variety of systemic diseases has a predisposition to involve the valvular structures of the heart. This chapter discusses connective tissue diseases, vasculitides, infiltrative cardiomyopathies, and other conditions. Diagnosis of amyloidosis by echocardiography includes increased thickness of the interventricular and interatrial septum, and both ventricles. A granular pattern of the myocardium has been proposed as a typical sign of this disease entity. Diastolic dysfunction is invariably present in almost all patients. Strain rate imaging allows documenting cardiac disease in its early stages, as it detects impairment of longitudinal contractile function. The most common valvular pathology encountered was regurgitation of aortic valve followed in descending frequency mitral regurgitation and rarely aortic stenosis.