Cardiovascular disease (CVD) is responsible for more deaths worldwide than any other condition, and a large proportion of healthcare budgets in more developed countries is spent on its treatment and prevention. In a period in which monetary resources for health care are limited and continue to be more and more restricted many studies have investigated the cost-benefit ratio of reducing blood pressure by considering patients’ characteristics and therapeutic options, to verify if it is possible to improve health outcomes and quality of life at a reasonable cost. Both conventional and newer strategies have been shown to be cost-effective relatively to various other medical interventions, but the latter seem to offer additional long-term benefits. Moreover, the differences in the impact of factors like poor compliance, switching and discontinuation of treatments may significantly affect the overall cost of antihypertensive therapy in clinical practice, and justify a better cost-effectiveness ratio for drugs like ARBs, ACE inhibitors and some CCBs despite their greater retail price. Future research should focus on long-term, real world, longitudinal studies to measure the actual costs and savings associated with increased compliance and persistence, and their impact on positive health outcomes, such as improved blood pressure.