The World Health Organization (WHO) has estimated that cardiovascular disease (CVD) is the number one cause of mortality globally, with more people dying annually from CVD than from any other cause. With as many as 17.7 million people dying from CVD in 2015, CVD represents 31% of all deaths worldwide. Moreover, over three quarters CVD deaths occur in low and middle-income countries, highlighting that this problem is not unique to industrialized nations. Accordingly, this special issue of the ATM provides perspectives on CVD not only in the United States (US), but also worldwide. We present a global, comprehensive view of innovative research, reviews, editorials and perspectives from basic science at the bench level to clinic interventions and public health considerations. While this edition of ATM builds on much of the research and clinical care conducted at Tulane University School of Medicine in New Orleans, Louisiana, USA, it also highlights provocative insights from other authors from the USA, along with articles from basic science researchers, clinicians and public health specialists from Africa, Europe, Asia and South America.