The reduction of large arterial distensibility has several adverse consequences for the cardiovascular system. This paper reviews the evidence we have obtained by measuring distensibility through quantification of changes in arterial diameter vs blood pressure changes at large elastic and middle size muscle artery sites. Evidence shows that arterial distensibility is reduced in conditions such as hypercholesterolemia, hypertension, diabetes, and congestive heart failure. In some conditions (e.g. hypertension) the alterations are not uniformly distributed in the arteries of different structure and size whereas in others (e.g. diabetes and heart failure) they are widespread. In diabetes evidence is available that distensibility changes occur early in the course of the disease. Evidence is also available that in all above conditions treatment can improve arterial distensibility thereby reversing the initial abnormality. This is due to a variable combination of structural and functional factors. However, technical ability to determine their precise role in distensibility changes in humans is limited.