Based on the SPRINT trial, it is highly likely that new SPRINT-era guidelines will establish a blood pressure (BP) goal of < 130/80 mm Hg for those aged 50 or older who are at high risk for a cardiovascular event. In this group, SPRINT demonstrated that assignment to an intensive-treatment systolic BP (SBP) goal of < 120 mm Hg significantly reduced cardiovascular events and mortality compared to those assigned to a standard-treatment SPB goal of < 140 mm Hg. This review critically assesses current hypertension guidelines and presents predictions for SPRINT-era guidelines in the elderly, African Americans, and patients with uncomplicated essential hypertension, diabetes, chronic kidney disease, cardiovascular disease, and coronary artery disease. Specific attention is paid to BP goals and preferred pharmacological antihypertensive therapy in these populations, and an algorithm that incorporates the SPRINT trial results is presented. Inhibitors of the renin-angiotensin-aldosterone system as well as calcium channel blockers are universally accepted as first-line therapy in uncomplicated hypertension, but controversy exists over the role of thiazide diuretics and beta blockers. This review also discusses a physiologically and outcomes-based approach to combination therapy for treatment of hypertension.