Fortunately, hypertension resistant to a good drug regimen is rare. When hypertension fails to respond to medical treatment there is usually another explanation, such as poor patient compliance, excessive salt ingestion, drug interactions, spuriously high office readings, or an unsuspected secondary cause for the hypertension. Management of resistant hypertension can be aided by identifying the hemodynamic and humoral mechanisms responsible for its resistance and redesigning the therapeutic regimens accordingly. When they become available, two investigational drugs, minoxidil and an oral converting enzyme inhibitor, both of which lower total peripheral resistance, will offer a new approach to controlling truly resistant hypertension.