The Sixth Joint Task Force of the European Society of Cardiology (ESC) and Other Societies on Cardiovascular Disease Prevention in Clinical Practice Guidelines have been published in 2016: greater emphasis has been placed on a population-based approach, on disease-specific interventions and on female-specific conditions, younger individuals and ethnic minorities. The ESC guidelines underscore that a lifetime approach to cardiovascular risk is important as both risk and prevention are dynamic and continuous. The guidelines can assist healthcare professionals, patients, and are valuable for the healthcare system but implementation of secondary cardiovascular disease prevention is far from optimal. Although there is no single way to ensure the use of guidelines in practice, multifaceted interventions based on known barriers are most appropriate. Essential components for implementation are: (a) taking action; (b) strengthening capacity; (c) evaluating impact; (d) advancing policy; and (e) engaging in regional and global partnerships. The strategy depends on a balanced investment in all available intervention approaches, from policy and environmental changes designed to prevent risk factors to assurance of quality care for individuals with cardiovascular disease. Our greatest challenges represent our greatest opportunities.