Despite the high prevalence of hypertension and documented benefits of blood pressure (BP) control, >40% of patients with hypertension are not controlled. A majority of uncontrolled hypertensive patients receive two or more antihypertensive drugs. The current review examined the relationship between antihypertensive combination drug therapy, achievement of goal BP, and cardiovascular (CV) outcomes. Articles were selected from a PubMed search using a prespecified search strategy. Randomized, controlled clinical trials of adult human subjects published in English between January 1991 and January 2013 were included. From 2319 identified articles, 28 met inclusion criteria and contained a total of 226,877 subjects. There were seven placebo-controlled studies and 21 treatment comparator and combination therapy studies. The studies included in this review reported a positive association between the degree of BP lowering, number of medications, and CV outcomes. As combination therapy became available, it was increasingly utilized in clinical trials and enabled an increased proportion of patients to achieve a prespecified BP target. Adverse events with monotherapy and combination therapy were as anticipated for the specific classes of antihypertensive therapy. Although many patients reach BP goal, combination antihypertensive therapy is often needed to reach BP goal. Effective BP lowering has been shown to result in improvements in CV outcomes.