Coronary stenosis severity is both a powerful and a still debated predictor of prognosis in coronary artery disease. Coronary computed tomographic angiography (CCTA) has emerged as a noninvasive technique that enables anatomic visualization of coronary artery disease (CAD). CCTA with newer applications, plaque characterization and physiologic/functional evaluation, allows a comprehensive diagnostic and prognostic assessment of otherwise low-intermediate subjects for primary prevention. CCTA measures the overall plaque burden, differentiates plaque subtypes, and identifies high-risk plaque with good reproducibility. Research in this field may also advance towards an era of personalized risk prediction and individualized medical therapy. It has been demonstrated that statins may delay plaque progression and change some plaque features. The potential effects on plaque modifications induced by other medical therapies have also been investigated. Although it is not currently possible to recommend routinely serial scans to monitor the therapeutic efficacy of medical interventions, the plaque modulation, as a part of risk modification, appears a feasible strategy. In this review we summarize the current evidence regarding vulnerable plaque and effects of lipid lowering therapy on morphological features of CAD. We also discuss the potential ability of CCTA to characterize coronary atherosclerosis, stratify prognosis of asymptomatic subjects, and guide medical therapy.