Most hypertensive patients will require more than one antihypertensive drug to lower BP below target levels. The combination of diuretics with renin-angiotensin system (RAS) antagonists offers several advantages to include additive BP-lowering efficacy and enhanced reductions in urinary protein excretion. Thiazide diuretics are associated with metabolic complications that are particularly evident when used in high doses. When used in combination with RAS blockade, metabolic complications such as hypokalemia are minimized. The avoidance of hypokalemia has been linked to less thiazide-induced glucose intolerance. Patient persistence on therapy is dependent on well tolerated drug combinations.