Distal embolization (DE) can be either spontaneous or iatrogenic, occurring during percutaneous coronary intervention (PCI). The nature, composition and biochemical properties of embolized material differ according to the setting in which DE occurs: acute coronary syndromes (ACS) or stable coronary artery disease (CAD). DE occurrence is related to increased cardiac biomarkers, negative left ventricular remodeling and associated with a poor prognosis. Prevention and treatment of DE represent some of the most debated topics in interventional cardiology. This review paper is focused on mechanisms of DE and on the strategies for its prevention and treatment in both ACS and stable CAD.