Intraluminal thrombus is a universal feature of acute coronary syndrome (ACS) as it is predominantly responsible for the accelerated process of vessel occlusion or subocclusion that characterizes the spectrum of ACS. Understanding the potential hazards that can be encountered when treating thrombotic lesions is crucial and being familiar with the strategies to deal with thrombus-containing lesion is mandatory for the interventional cardiologist. Initial management requires include: (i) recognition of the presence of thrombus and its quantification, (ii) understanding that a thrombus-containing lesion is unpredictable and prone to sudden evolution with consequent patient's rapid hemodynamic deterioration, (iii) understanding that thrombus and debris can embolize distally downstream of the coronary microcirculation, blunting the benefit of revascularization, (iv) being aware that thrombotic lesions are usually associated with high vascular tone and this, together with the presence of thrombotic debris, presents challenges to optimal stent sizing, with consequent increased risks of stent under-sizing and/or malapposition. This chapter describes an interventional approach to managing thrombus-containing coronary lesions.