Staphylococcus aureus bacteremia (SAB) is a serious and growing problem. A longstanding controversy in infectious diseases has centered around the duration of therapy for patients with SAB. Fortunately, the refinement of echocardiography and the creation of new diagnostic criteria have aided in the diagnosis of infective endocarditis in patients with SAB. These advancements have resulted in the development of an algorithm that combines clinical, microbiologic, and echocardiographic findings to stratify patients with SAB into different treatment regimens.