New diagnostic techniques have now become available that will enable us to obtain information on coronary artery disease (CAD), which was not previously possible. This is urgently needed, since changes in CAD management are highly desirable considering that up to 60% of patients die due to an insufficient diagnostic strategy (reactive strategy). In this article, the pathophysiology of CAD and the evidence of current concepts on coronary atherosclerosis are critically reviewed. Consequently, a shift from a 'reactive strategy' of CAD management to an active strategy is proposed in order to detect and treat patients before acute myocardial infarcts occur. Reliability, repeatability, cost-effectiveness and comfort are important features of an optimal test for this active strategy. This perspective gives an overview of current and future tests with respect to these features. The novel tomographic techniques are particularly promising with respect to standardization and reproducibility, which will set the basis for the determination of test performance and, consequently, cost-effectiveness. Assessment of cost-effectiveness is increasingly important, since prevalence of CAD is high and will most likely increase, while resources will remain restricted in most countries. Considering these economic restrictions, this article also proposes new mathematical tools using data from prospective trials and large international registries as an objective means to select the best tests for CAD diagnosis and management, and to identify those patient subsets which benefit most from an active strategy.