After the observation that distal embolization is a frequent complication of coronary and vascular interventions, mechanical emboli protection devices (EPD) have been developed and tested in different vascular territories. The most frequently used device type incorporates a guidewire with a filter that is placed distal to the target lesion, unfolded, and then retrieved at the end of the procedure. Alternative approaches are based on transient flow obstruction using proximal or distal balloon occlusion. The procedure is then performed under flow reversal or flow arrest and the blood column is evacuated prior to restoration of flow. The efficacy of EPD in reducing major adverse cardiac events among patients undergoing percutaneous intervention of aortocoronary bypass grafts has been demonstrated in a randomized trial. In the acute myocardial infarction setting, EPD failed to improve outcomes. Although randomized data in carotid artery stenting are lacking, a broad, but not unanimous, consensus supports the use of these devices. While a small randomized trial showed disappointing results of emboli protection in renal stenting, no data are available for lower extremity interventions.