Infective endocarditis is associated with significant cardiac and noncardiac morbidity. Among many complications, septic embolism has the potential of causing devastating sequelae and even life-threatening clinical situations. This dreaded clinico-pathologic entity is characterized by its heterogeneous presentation and the ability to affect various body systems and organs. Septic emboli to the brain, kidneys, spleen, and the pulmonary system constitute the vast majority of metastatic infections. However, other organ systems can also be affected. This chapter provides an overview of septic embolism associated with infective endocarditis, focusing on key diagnostic and therapeutic considerations in the most commonly seen and clinically relevant scenarios.