Patient safety improvement initiatives are often chosen in the context of an existing tension between taking an evidence-based approach versus a practical one. This commentary provides a framework for choosing various interventions with a particular focus on what hospitalists should target for implementation. The authors advocate for a "balanced diet" approach in combining: (1) important practices with strong evidence (e.g., prevention of catheter-related blood stream infections), (2) momentum-generating projects (e.g., executive walk rounds), and (3) system-level interventions (e.g., computerized physician order entry [CPOE]). A previous AHRQ WebM&M perspective addresses how to interpret the patient safety literature.