Strategies to prevent medication errors are an ongoing focus in patient safety. Computerized provider order entry, medication reconciliation, avoidance of drug–drug interactions, and bar-coded medication administration are a few areas generating significant attention. This review discusses an alternate approach to medication safety, focusing on prevention of prescribing unnecessary medications at the outset. The authors provide a set of principles that urge clinicians to: think beyond drugs, practice more strategic prescribing, maintain heightened awareness about side effects, exercise skepticism about new drugs, work with patients for a shared agenda, and consider long-term impacts of medications prescribed. Each of these principles is discussed and sets the background for a recommendation to shift current paradigms in prescribing from "newer and more is better" to "fewer and more time tested is best."