Increases in arterial blood pressure cause cumulative changes in tissue structure and function, resulting ultimately in end-organ damage. One of the pathological hallmarks of hypertensive tissue injury is an increase in tissue fibrosis, which leads to reductions in tissue compliance and function. Fibrosis (or sclerosis) occurs as result of marked changes in the amount and composition of the extracellular matrix. This extracellular matrix is a complex mixture of structural proteins and glycoproteins, including collagens, fibronectins, and proteoglycans. Hypertension is known to be associated with increases in the synthesis of extracellular matrix proteins and changes in their degradation. These processes are mediated by several mediators, in particular the renin-angiotensin-aldosterone system. Since these changes play an important role in the formation of vascular sclerosis, cardiac dysfunction, and renal damage, understanding the mechanisms, and finding interventions to prevent or reverse these changes are clinically important. In this review we discuss the alterations in the extracellular matrix during hypertension, as well as the effects of antihypertensive agents in animal models and human patients.