The clinical presentation of patients with Staphylococcus aureus bacteraemia (SAB) varies from uncomplicated bacteraemia to a fulminant or deep-seated infection. To assess the clinical presentation and outcome and to detect possible flaws in management of these patients, a retrospective study was conducted including 75 adult patients with SAB admitted to a university hospital in The Netherlands between July 1999 and December 2000. In 26 of the 75 (35%) patients, SAB was complicated by a deep-seated infection. In 2 patients the diagnosis of infective endocarditis was missed. The overall mortality rate was 23%. In 10 (13%) patients death could be directly ascribed to SAB. In 3 of these 10 patients antimicrobial treatment had been inadequate. Relapse of infection occurred in 9 (12%) patients. Seven of these 9 patients were treated inadequately during the first infectious period. Two of the 9 patients died and another 2 suffered serious complications during relapse of infection. These findings stress the need for consultation of infectious disease specialists in management of patients with SAB and the urgent need for standardization and a guideline considering the approach of a patient with SAB. A proposal for such a guideline is presented in this manuscript.