With ongoing progress in the prevention and treatment of coronary artery disease (CAD), a continued decrease in prevalence and lethality is expected in high-income countries. Prevention will include lipid-lowering, antithrombotic and anti-inflammatory therapies. With respect to the former, potent, safe and prolonged drugs (such as generic forms of PCSK9 inhibitors relying on monoclonal antibodies or miRNA) should result in a decreased incidence of acute coronary syndromes. Another key aspect will be the ability to identify genetic predictors of CAD and therefore implement targeted personalized prevention early in life. Curative treatment will involve a short course of potent and reversible antithrombotics, but long-term therapy will rely on the ability to stabilize or even regress plaque (eg, using PCSK9 inhibition or modified high-density lipoprotein infusions or anti-inflammatory therapies). Antithrombotic therapy will rely on highly reversible agents (or agents with specific titratable antagonists), and on personalized therapies in which the doses, combinations and duration of therapy will be determined differentially for each patient on the basis of clinical characteristics, genetic profiling and biomarkers. Finally, the need for revascularization in stable CAD will be rare, given the expected progress in prevention. The main challenge, 20 years from now, is likely to be the provision of such effective care at acceptable costs in low- and middle-income countries. (Circ J 2016; 80: 1067-1072).