Hospitalists play an important role in improving patient safety through clinical expertise and leadership in hospital quality improvement activities. The evidence base in patient safety remains incomplete, despite an increasing body of published research in recent years. Thus, physicians must consider other factors in addition to the strength of evidence supporting a practice when deciding which patient safety interventions to implement. These factors include the prevalence of the safety problem targeted, the potential for unintended consequences of the intervention, the costs and complexity of implementing the intervention, and the potential of the intervention to generate momentum for further safety initiatives. In this article, the authors define a framework for evaluating patient safety interventions and discuss specific interventions hospitalists should consider.