The prevalence and incidence of End-Stage Renal Disease (ESRD) have progressively increased in the last 20 years. Hypertension and diabetes are the two most important causes of ESRD, and antihypertensive treatment plays a crucial role in preventing Chronic Renal Failure (CRF) and ESRD. The glomerulus and mesangial extracellular matrix are the principal sources giving rise to hypertensive nephropathy, which is finally characterized by progressive glomerulosclerosis. Several mechanisms are involved in hypertensive nephropathy, including increases in intraglomerular pressure and extracellular matrix production and reactive oxygen species (ROS)-related damage. The various activities of antihypertensive drugs on the kidney are particularly important in understanding their nephroprotective role and in developing new nephroprotective pathways in the future. This paper reviews the main pathophysiological aspects of renal damage in hypertension, the effects of various types of calcium channel blockers (CCBs) on renal function, and their role in nephroprotection.