Although the true prevalence of resistant hypertension is not known, it is likely that this condition will become increasingly common, driven by an aging population, obesity, nonadherence trends, and effects of target-organ disease. Current approaches focus on two goals: evaluation and correction of contributing causes, then selection of an effective drug regimen. Lifestyle factors contribute to resistance, particularly high sodium intake and weight gain. Secondary causes should be considered and corrected if feasible. Recent efforts have focused on the development of clinical pathways to guide treatment, based on plasma renin activity, aldosterone production, or hemodynamic measurements. The components of drug combinations beyond the second agent remain empiric. Although volume expansion plays a key role in drug resistance, clinical assessment of volume status is often difficult, frustrating efforts to achieve blood pressure control. Determination of the most effective approaches will require clinical trials using combination therapy.