Traditional targets for antihypertensive therapy include vascular smooth muscle and endothelium, the renin/angiotensin and sympathetic nervous systems, and the renal tubules. The progressive improvement in efficacy and tolerability of antihypertensive pharmacotherapy has depended largely on development of agents that target multiple control mechanisms. For example, angiotensin converting enzyme inhibitors (and angiotensin receptor antagonists) act at all of these physiological targets. Recent basic research has identified new potential targets for antihypertensive therapy, particularly within the kidney, which should be considered both in terms of their responses to available antihypertensive agents, and in the development of newer, more effective agents. For example, there is now new information about how alterations in structure and function of the renal circulation can contribute to the development of hypertension, by causing dysregulation of glomerular filtration and renal medullary perfusion, and so the ability of the kidney to regulate salt and water balance. There is also increased understanding of how reactive oxygen species can contribute to cardiovascular disease, particularly that associated with diabetes. This new information raises the exciting possibility of future development of agents that actually target the underlying causes of hypertension, with the potential to provide prophylaxis or cure, rather than just maintenance therapy.