Improvements in hypertension treatment and control are challenged by the increasing incidence of metabolic risk factors for hypertension, in particular, obesity and insulin resistance. Such risk factors can increase the severity of hypertension and can interact via a multitude of hormonal and inflammatory pathways. Their presence may affect antihypertensive agent choice with regard to antihypertensive efficacy as well as potential synergistic or antagonistic effects on inflammatory status and progression to diabetes. Furthermore, an increasing number of pharmacologic options are available to promote weight loss and insulin sensitivity that may affect blood pressure directly and indirectly. This review considers the metabolic basis for the complex interactions of hypertension with obesity and insulin resistance, and it assesses the clinical evidence for an impact of weight loss and insulin-sensitizing treatment on blood pressure. Awareness of these pathophysiologic interrelations and their implications for treatment are likely to be of increasing importance for successful blood pressure management.