Even today, in times of modern antibiotic therapy, infective endocarditis is a disease with a high mortality which is difficult to diagnose and to treat. The changing clinical face of this disease in the last decades results from a changing predisposition of the patients, an increasing age, and is accompanied with shift from streptococci toward staphylococci as the main causative microorganisms. Evidence from randomized trials is limited due to a low incidence of the disease. Thus, application of the guidelines for diagnosis and treatment on a patient has always to respect the individual history, and the individual clinical course. The authors describe and comment the case of a patient with endocarditis of the native aortic valve due to S. epidermidis from diagnosis to discharge from the hospital following the current German guidelines for diagnosis and treatment of infective endocarditis.