The reduction in polypharmacy and avoidance of inappropriate medications is a common goal in the care of older persons, regardless of setting. While multidisciplinary teams and regular medication reconciliation and review can identify and reduce medication-related problems, tools to decrease the use of high-risk/low benefit medications can help the individual clinician to improve prescribing. Numerous criteria, tools, algorithms, and scoring systems have been developed for use in a wide range of areas from long-term care to the outpatient setting, and some may not be applicable to individual situations. Not all medication review instruments have been adequately validated, and the tools we have presented have varying levels of evidence to support their use. Clinicians also need to be aware of regulatory, policy, and guideline issues that may impact the use of certain criteria for optimum prescribing. Ultimately, optimizing prescribing by reducing polypharmacy and avoiding inappropriate medications is a highly individualized process for each patient, and clinicians will have to use extensive clinical judgment in using the tools presented here.