Infective endocarditis (IE) is estimated to have an incidence of five to seven cases per 100,000 person-years. Although not a common clinical entity, IE is associated with substantial morbidity and risk of mortality. IE, especially infections due to Staphylococcus aureus, are increasingly healthcare-associated infections. Despite significant advances in diagnosis and management, mortality from IE has changed little since the availability of penicillin; however, this lack of improvement in mortality is likely due to an increasing number of infections from more virulent and drug-resistant pathogens coupled with infections that occur in patients with other comorbidities and those associated with prosthetic valves. Surgery is an important part of therapy for many patients, but surprisingly, little evidence is available to help clinicians determine which patients will benefit most from surgical therapy for the management of IE.