Polypills can contain multiple pharmaceutical agents targeting the cardiovascular system. The use of polypills in the secondary prevention of cardiovascular disease (CVD) has received broad support; however, the use of polypills in the primary prevention of CVD is more controversial. This controversy stems from an inherent resistance to the medicalization of primary prevention, and the lower CVD event rate in this population means that smaller absolute benefits are derived. Indeed, drug-related adverse effects, such as from aspirin, might even outweigh the benefits. The role of fixed-dose combination (FDC) therapy for blood pressure (BP) lowering in combatting the widespread under treatment of high BP — the leading modifiable risk factor contributing to the global burden of CVD — has gained momentum. Increasing evidence suggests that FDC pills containing multiple low doses of BP-lowering drugs produce more effective BP lowering than the use of fewer separate BP-lowering drugs at higher doses, without an increase in adverse effects.