Cardiovascular disease (CVD) has become the most common cause of mortality worldwide. Obesity, insufficient physical exercise, diabetes, and advancing age are major risk factors for developing cardiovascular disease that are currently increasing in prevalence. Nevertheless, significant progress has recently been made in the treatment of complex cardiovascular and coronary artery disease (CAD), with pharmacological management set to assume an increasingly important role. Other timely factors, such as the development of the polypill and high-level medical and political interest in advancing cardiovascular health, are driving forces that may help to make inroads into the global cardiovascular disease burden. In this article, we critically review the key challenges that we face in the coming decade as we strive to transition and apply our growing knowledge of complex CAD to promoting global cardiovascular health.