The current duration of therapy in patients with Staphylococcus aureus bacteremia (SAB) is based on differentiating complicated from uncomplicated disease. While this approach allows clinicians and investigators to group SAB patients into broadly similar clinical categories, it fails to account for the intrinsic heterogeneity of SAB. This is due in part to the fact that risk factors for metastatic infection and confirmed metastatic infection are considered as equivalent in most scoring systems. In this viewpoint, we propose a two-step system of categorizing patients with SAB. Initially, patients with SAB would be categorized as ‘high risk’ or ‘low risk’ for metastatic infection based upon an initial set of diagnostic procedures. In the second step, patients identified as ‘high-risk’ would undergo additional diagnostic evaluation. The results of this stepwise diagnostic evaluation would define a ‘final clinical diagnosis’ to inform an individualized final treatment plan.