Percutaneous coronary intervention (PCI) is an expanding treatment option for patients with coronary artery disease (CAD). It is considered the default strategy for unstable presentation of CAD. PCI techniques have evolved over the last 4 decades with significant improvements in stent design, increase in functional assessment of coronary lesions, and the use of intra-vascular imaging. Nonetheless, the morbidity and mortality related to CAD remain significant. Advances in technology have allowed better understanding of the nature andprogression of CAD. New tools are now available that reflect the pathophysiological changes at the level of the myocardium and coronary atherosclerotic plaque. Certain changes within the plaque would render it more prone to rupture leading to acute vascular events. These changes are potentially detected using novel tools invasively, such near infra-red spectroscopy, or non-invasively using T2 mapping cardiovascular magnetic resonance imaging (CMR)and18F-Sodium Fluoride positron emission tomography/computed tomography. Similarly, changes at the level of the injured myocardium are feasibly assessed invasively using index microcirculatory resistance or non-invasively using T1 mapping CMR. Importantly, these changes could be detected immediately with the opportunity to tailor treatment to those considered at high risk. Concurrently, novel therapeutic options have demonstrated promising results in reducingfuture cardiovascular risks in patients with CAD. This Review article will discuss the role of these novel tools and their applicability in employing mechanical and pharmacological treatment to mitigate cardiovascular risk in patients with CAD.