This article discusses the recently published EMPA-REG OUTCOME trial, which assessed cardiovascular outcomes with empagliflozin therapy in persons with type 2 diabetes mellitus and coexisting cardiovascular disease. The article describes the background and challenges of modern cardiovascular outcome trials, points out the strengths of the EMPA-REG OUTCOME study, and places the results in perspective. It highlights the significant impact that these results will have on cardiovascular preventive pharmacotherapy, and on future drug development in diabetes. At the same time, it reminds readers of the limitations of the results, and lists the questions raised by, or left unanswered by, the trial.