Despite years of investigation our fundamental and clinical knowledge of the major public health problem, obesity-hypertension, is relatively meager and certainly inadequate. We are at a loss to explain why the pathophysiological mechanisms of obesity and hypertension are so inextricably intertwined. Adding to this frustration is the inadequacy of the treatment for obesity. Hemodynamically, we recognize that the expanded plasma volume caused by obesity imparts a significant volume overload on the heart, thereby increasing cardiac output, while the hypertension compounds this ventricular stress by an associated pressure overload. Thus, the ventricle has an eccentric as well as a concentric adaptive hypertrophy. Associated with obesity is an increased burden of pressor (e.g., catecholamine, angiotensin II); peptide (e.g., endothelin, insulin, leptin, natriuretic); hormonal (e.g., growth, steroids, thyroid); and neural mechanisms. Further complicating these alterations are electrolytic, lipid, uric acid, and other metabolic factors. Both diseases (obesity and hypertension) are exacerbated by frequently encountered comorbid pathophysiological disorders including atherosclerosis, ventricular dysfunction, diabetes mellitus, hyperlipidemias, and sleep apnea. To add to these issues, therapy for obesity-hypertension is suboptimal. Behavioral modification (of overweight and obesity) is commonly characterized by recidivism, and pharmacotherapy of obesity is woefully inadequate; the present agents either raise arterial pressure or are fraught with adverse effects. Fortunately, there are no contraindications imparted by obesity that complicate the drug treatment of the associated hypertension. Each of the lifestyle modifications and seven classes of antihypertensive therapy that is discussed herein is done in light of the coexistent hypertension and comorbid diseases.