Most infective processes are straightforward and can be diagnosed from bacterial findings in a single test. IE does not always follow this tenet, so establishing the diagnosis can be difficult. The salient features of IE may present atypically or be obscured by the presence of preexisting and coexisting diseases. Flulike symptoms may mask the beginning of this devastating disease. Early diagnosis of IE is important because of its high risk of morbidity and mortality. Management of the patient who has IE is complex and requires interventions by infectious disease specialists, cardiologists, respiratory therapists, and critical care nurses to address the many multifaceted complications. Early evaluation, diagnostic validation, multidisciplinary management, prompt pharmaceutical initiation, and intense critical care nursing intervention are necessary to reduce the probability of long-standing complications and to improve patient outcomes.