<p>Cardiovascular disease (CVD) has achieved pandemic proportions and is currently the leading cause of death worldwide. Barriers to optimal secondary cardiovascular prevention include lack of access to chronic treatment as well as low adherence in those who receive these treatments. The polypill represents a simple, cost-effective, scalable strategy to improve access and adherence to medication and effectively bridge the current gap in secondary prevention of CVD. Here, we review the epidemiological need for such a strategy as well as the most notable clinical evidence reported in the past decade supporting the clinical use of the polypill. Furthermore, we discuss the barriers inherent to the acceptance and use of the polypill for secondary prevention of CVD compared to the uptake of other polypills for the treatment of communicable diseases where fixed-dose combinations have become accepted as the cornerstone of treatment for other global pandemics such as HIV.</p>