Background: This systematic review summarizes the benefits of treating blood pressure (BP) in individuals 65 years and older. Methods: We included randomized trials that evaluated BP-lowering medications or BP targets in individuals 65 years and older. Trials were selected and appraised by pairs of independent reviewers. Results: We included 19 trials (42,134 patients). In individuals 65 years or older, antihypertensive therapy was associated with a reduction in all-cause mortality [relative risk: 0.88 (95% CI: 0.81 to 0.94); high certainty evidence; mean follow-up 31 months], cardiovascular mortality, myocardial infarction, heart failure, stroke, and chronic kidney disease. Individuals 75 years or older had a significant reduction in the risk of all-cause and cardiovascular mortality, stroke, and heart failure. Strict systolic BP targets (,120 mm Hg and ,130 mm Hg) were associated with a significant reduction in the risk of all-cause and cardiovascular mortality and heart failure, whereas more liberal systolic targets (,150 mm Hg and ,160 mm Hg) were associated with lower risk of heart failure and stroke. Older adults with type 2 diabetes mellitus (DM) had lower risk of chronic kidney disease without a significant reduction in other outcomes. However, there was no significant difference in estimates (i.e., interaction) between those with and without DM. Conclusions: Individuals aged 65 years and older or 75 years and older who receive antihypertensive therapy have statistically significant reduction in the risk of all-cause and cardiovascular mortality, heart failure, and stroke. There was no statistically significant difference in estimates between those with and without DM.