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Recently, there has been a growing interest in identification of coronary “vulnerable plaques” that are prone to rupture; this potentially would help identify patients with higher risk of development of cardiac events. Recent advances in cardiac imaging modalities have been successful in studying various plaque vulnerability features to variable degrees, strengths and limitations. Computed Tomography Coronary Angiography (CTCA) has gained an increasing popularity in studying plaque anatomy, morphology and composition by the virtue of its widespread availability and non-invasiveness. CTCA has been validated against histology and IVUS with reasonable correlation; moreover, some follow-up studies have shown a significant association to the development of acute coronary syndromes. Nevertheless, attention should be paid to the whole patient big picture that includes other factors operating on other extra-coronary axes that involve inflammation, immunity, coagulation and neuroendocrine systems.