It is evident that blood pressure reduction per se is the primary determinant of cardiovascular risk reduction. Available data suggest that at least 75% of patients will require combination therapy to achieve contemporary blood presure targets, and increasing emphasis is being placed on the practical tasks involved in consistently achieving and maintaining goal BP in clinical practice. This review 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.