Polypill is a fixed-dose combination of medications with proven benefits for the prevention of cardiovascular disease (CVD). Its role in CVD prevention has been extensively debated since the inception of this concept in 2003. There are two major kinds of polypills in clinical studies. The first is polypill that combines multiple low-dose medications for controlling only one CVD risk factor (such as high blood pressure or high serum cholesterol). These "single-purpose" polypills were mostly developed from original producers and have higher cost. The polypill that combines 3-4 pharmaceutical components, each with potential to reduce one major cardiovascular risk factors is "multi-purpose" or "cardiovascular" polypill. Using data from various clinical trials and from meta-analysis, Wald and Law claimed that this "cardiovascular" polypill when administered to every individual older than 55 years could reduce the incidence of CVD by more than 80%. Several short and intermediate to long-term studies with different cardiovascular polypills in phase II and III trials showed that they could provide better adherence, equivalent, or better risk factor control and quality of life among users as compared to usual care. One recently published randomized controlled clinical trial demonstrated the effectiveness and safety of a four-component polypill for both primary and secondary CVD prevention with acceptable number needed to treat (NNT) to prevent one major cardiovascular event. Considering the slow achievement of CVD prevention in many poor- and middle-income Asian countries and also the need to further improve compliance of antihypertensive and lipid lowering medications in many high-income Asian countries, the concept of "cardiovascular polypill" could be very useful. With further support from ongoing polypill cardiovascular outcome trials, polypill could be the foundation of the population-based strategies for CVD prevention.