Editor’s Note: The American Society of Hypertension is publishing a series of Position Papers in their official journals throughout the 2008–2011 years. The following Position Paper originally appeared: JASH. 2010;4:42–50.The goal of antihypertensive therapy is to abolish the risks associated with blood pressure (BP) elevation without adversely affecting quality of life. Drug selection is based on efficacy in lowering BP and in reducing cardiovascular (CV) end points, including stroke, myocardial infarction, and heart failure. Although the choice of initial drug therapy exerts some effect on long‐term outcomes, it is evident that BP reduction per se is the primary determinant of CV risk reduction. Available data suggest that at least 75% of patients will require combination therapy to achieve contemporary BP targets, and increasing emphasis is being placed on the practical tasks involved in consistently achieving and maintaining goal BP in clinical practice. It is within this context that the American Society of Hypertension presents this Position Paper on Combination Therapy for Hypertension. It will address the scientific basis of combination therapy, present the pharmacologic rationale for choosing specific drug combinations, and review patient selection criteria for initial and secondary use. The advantages and disadvantages of single‐pill (fixed) drug combinations and the implications of recent clinical trials involving specific combination strategies will also be discussed. J Clin Hypertens (Greenwich). 2011;13:146–154. © 2010 Wiley Periodicals, Inc.