The concept of the vulnerable plaque has generated much interest and stimulated a quest to develop diagnostic modalities to identify potentially unstable atherosclerotic plaques. However, accumulating clinical data now suggest that multiple vulnerable plaques coexist in a single coronary tree and that inflammation is a critical determinant of the stability of plaques. Inflammatory mediators, such as cytokines, can influence several biologic processes that regulate stability of the plaque's fibrous cap and its resistance to rupture. Thus, the quest for strategies to identify and target treatment to a single culprit lesion seriously underestimates the complexity of the clinical biology of thrombosis in atherosclerotic arteries. For the optimum management of our patients, we must now also consider the vulnerable artery, the vulnerable arterial bed, and ultimately, the vulnerable patient. Treatment of vulnerable patients should include measures to stabilize plaques and to lessen the thrombotic consequences of plaque disruptions.