The prevalence of obesity is steadily increasing. Hypertension is one of the most common co-morbidities of obesity and significantly contributes to morbidity and mortality. Most obese hypertensive patients require antihypertensive drug treatment. However, current guidelines do not give specific recommendations for antihypertensive therapy of obese hypertensive patient. Some antihypertensive agents may have unwanted effects on the metabolic and hemodynamic abnormalities that link obesity and hypertension. Due to the lack of guidelines, this chapter provides recommendations for or against each class of antihypertensive agents mostly based on subjective criteria and pathophysiologic assumptions. Diuretics and betablockers are reported to reduce insulin sensitivity and increase lipid levels, whereas calcium antagonists are metabolically neutral and ACE-inhibitors as well as angiotensin receptor blockers increase insulin sensitivity. Sodium retention plays a central role in the development of obesity-related hypertension. Therefore, treatment with an ACE-inhibitors or a diuretic should be considered as first-line antihypertensive drug therapy in obesity-hypertension.