Ischemic heart disease and stroke are the leading causes of death worldwide. A large proportion of individuals at high 10-year risk of a cardiovascular event live in low-income and middle-income countries, and the large majority of all cardiovascular events occur in developing countries. A large amount of evidence supports the use of pharmacological treatment for the prevention of cardiovascular death in this population, including antiplatelet drugs, beta blockers, lipid-lowering agents and angiotensin-converting-enzyme inhibitors. However, the efficacy of cardiovascular prevention is hampered by several problems, including inadequate prescription of medication, poor adherence to treatment, limited availability of medications and unaffordable cost of treatment. Here we examine the use of fixed-dose combination therapy (a 'polypill'), and how this therapy could improve adherence to treatment, reduce the cost and improve treatment affordability in low-income countries.