Contemporary clinical evaluation of hypertensive patients must include observations encompassing the impact of environment, behavior, and sociologic factors on metabolism and physiology. As evidenced by animal and human studies, catecholamines are an important mediator between psychologic factors and cardiovascular physiology, but direct measurement of catecholamine levels has not proved useful. Measurement of hemodynamic variables—blood pressure, heart rate, and stroke volume—during standardized psychophysiologic challenges is advocated. With low-challenge standardized stressors that include α- and β-adrenergic stimuli, inappropriate reactors can be classified according to whether blood pressure is elevated primarily by cardiac output, total systemic resistance, or a combination of both. Hypertensive patients can be similarly distinguished, and medication can then be custom-tallored to the underlying physiology. Extensive laboratory and clinical evidence points to significant interrelationships between the central nervous system and the cardiovascular system. Furthermore, cardiovascular physiologic and metabolic perturbances are distinctly different under conditions of mental vs physical stress. Most clinical testing assesses physical performance whereas the real-life challenges of today are primarily mental.