Despite improved diagnostic tools and expanded treatment options, left-sided native valve endocarditis caused by Staphylococcus aureus infection remains a serious and destructive disease. The high morbidity and mortality, however, can be reduced by early recognition, correct diagnosis, and appropriate treatment. In the following article, we discuss the clinical presentation, diagnostic workup and treatment of infective endocarditis, thereby reviewing the current guidelines. Blood cultures and echocardiography are the cornerstones of diagnosis in identifying infective endocarditis but are no substitute for clinical judgement. The modified Duke criteria may facilitate the diagnostic process, but clinical evaluation remains crucial.