Older adults with chronic kidney disease (CKD) often experience polypharmacy, a recognized predictor of prescribing problems including inappropriately dosed medications, drug-drug and drug-disease interactions, morbidity and mortality. Polypharmacy is also associated with nonadherence, which leads to recurrent hospitalizations and poorer hemodialysis outcomes in CKD patients. Further complicating medication management in this vulnerable population are the physiologic changes that occur with both age and CKD. This guide for pharmacists and prescribers offers considerations in medication evaluation and management among older adults with CKD. Careful prescribing with the aid of tools such as the American Geriatrics Society Beers Criteria can support safe medication use and appropriate prescribing. Polypharmacy may be systematically addressed through 'deprescribing,' an evidence-based process that enables identification and elimination of unnecessary or inappropriate medications. Detailed guidance for deprescribing in older adults with CKD has not been published previously. We highlight three specific targets for medication optimization and deprescribing in older adults with CKD: (1) proton pump inhibitors, (2) oral hypoglycemic agents, including newer classes of agents, and (3) statins. These medication classes have been chosen as they represent three of the most commonly prescribed classes of medications in the United States. For each area, we review considerations for medication use in older adults with CKD and provide strategies to avoid, modify, or discontinue these medications when clinically indicated. By utilizing deprescribing techniques, pharmacists are well positioned to help decrease the medication burden in older adults with CKD, thereby potentially reducing the risk of morbidity and mortality associated with polypharmacy.