Ischaemic heart disease, stroke, and other cardiovascular diseases (CVDs) are responsible for an estimated 17.5 million annual deaths in the world. If account is taken of population aging, death rates from CVDs are estimated to be steadily decreasing in the world as a whole, and in regions with reliable trend data. The declines in high-income countries and some countries in Latin America have been ongoing for decades with no indication of slowing. In high-income countries, these positive trends have broadly coincided with, and benefited from, declines in smoking and physiological risk factors like blood pressure and serum cholesterol. Improvements in medical care, including effective primary prevention through management of physiological risk factors, better diagnosis and treatment of acute CVDs, and post-hospital care of those with prior CVDs, are also likely to have contributed to declining CVD event and death rates, especially in the past 40 years. However, the measured risk factor and treatment variables neither explain why the decline began when it did, nor much of the similarities and differences in the start time and rate of the decline across countries or between men and women. There have been sharp changes and fluctuations in CVDs in the former communist countries of Europe and the Soviet Union since the fall of communism in the early 1990s, with changes in volume and patterns of alcohol drinking, as a major cause of the rise in Russia and some other former Soviet countries. The challenge of reaching more definitive conclusions concerning the drivers of what constitutes one of the most remarkable international trends in adult mortality in the past half-century in part reflects the paucity of time trend data not only on disease incidence, risk factors, and clinical care, but also on other potential drivers, including infection and associated inflammatory processes throughout the lifecourse.