In this article, the author identifies the major causes of difficult-to-treat hypertension and provides guidelines for its management. The data were obtained from multiple clinical series of patients with hypertension resistant to therapy, reports of over-sensitivity to antihypertensive drugs, and the effects of anxiety-induced hyperventilation. As many as 15% of patients are resistant to antihypertensive therapy. Of the multiple possible causes for resistance, volume overload is the most common. Volume overload, in turn, is related to multiple factors, with inadequate diuretic therapy playing a major role. Many patients may experience tissue hypoperfusion when given usual doses of antihypertensive therapy, making their hypertension difficult to treat. In the author's experience, an even larger number of patients have psychosomatic symptoms, usually attributable to anxiety-induced hyperventilation, that often are blamed on their therapy. Therefore, hypertension may be difficult to treat for various reasons. When the cause is recognized, appropriate management almost always can be provided.