Deciding who to treat should be based on estimation of the total cardiovascular risk, not just the blood pressure (BP), so that patients with established cardiovascular disease or at high risk of cardiovascular disease should have their BP lowered even though it may be in the "normal range". Drug treatment should build upon effective lifestyle measures. Meta-analyses from the Blood Pressure Lowering Treatment Trialists' Collaboration have shown that differences between drug classes are quite small, even across different age groups, compared to the benefits of maximizing the reduction in BP, especially the systolic pressure. The major guidelines now recommend a focus on building effective drug combinations rather than arguing about which drug to use, and they approve initiation of treatment with combinations in high risk groups. While clinical trials have demonstrated some differences in the efficacy of individual drug classes in reducing cause specific outcomes such as coronary disease, stroke or heart failure, there are still very few comparisons between drug combinations. Our own preferred combinations include angiotensin converting enzyme inhibitors (ACEI) and diuretics, which comprise my first choice for Caucasians and Asians, and angiotensin receptor blockers (ARB) which are best used with diuretics when ACEI are not tolerated. ACEI and calcium channel blockers (CCB) are also very effective and CCB and diuretics are preferred for black subjects or those with isolated systolic hypertension. Combinations to avoid in patients with uncomplicated hypertension include ACEI and beta-blockers and ACEI and ARBs, since their beneficial effects are not additive.