Infective endocarditis remains a disease associated with high mortality in certain groups of patients, with death resulting primarily from central nervous system complications and congestive heart failure. Combined medical and surgical therapy reduces both early and late mortality in complicated cases, especially in patients with valvular dysfunction related to heart failure. In these patients, heart failure is the strongest indication for valve replacement. There are no consensus indications for surgery, however, in the presence of neurological complications or multiple organ failure. Limited data suggest that such surgery is feasible, even in complicated cases necessitating admission to the intensive care unit, and carries an acceptable risk for in-hospital mortality. It is important that critically ill patients with infective endocarditis are enrolled into multicenter studies, using adequate severity scoring systems to assess the impact of clinical and imaging variables on patients' outcome. Until such data are obtained, clinical judgement is still the best tool in decision-making regarding the individual patient.