Patients with dementia experience high rates of polypharmacy, potentially inappropriate medication use, and adverse drug events. There is little guidance for clinicians on how to optimize prescribing for this population. Our objective was to investigate clinician-perceived barriers to and facilitators of optimizing prescribing for people with dementia. Methods: Qualitative study involving semistructured interviews of primary care and specialist clinicians in urban, suburban, and rural settings. Transcripts were analyzed using qualitative content analysis. Results: Interviews were conducted with 12 primary care and 9 specialist clinicians, with a mean (SD) age of 47 (9) and mean (SD) of 14 (10) years in practice. Clinicians cited decisions regarding the following drug classes as particularly challenging: oral anticoagulants, antidiabetic agents, statins, bladder antimuscarinics, and antipsychotics. Perceived enablers of optimizing prescribing included access to interdisciplinary services and guidelines for nondementia illnesses (eg, diabetes) addressing the care of people with dementia. Barriers included the lack of data on efficacy and safety of most medications in people with dementia, difficulty assessing medication effects in an individual patient, and the perception that stopping medications is seen as "giving up." Clinicians used a variety of strategies to discuss risks and benefits of medications with patients and caregivers. Conclusions: Clinicians identified numerous barriers to and some facilitators of optimizing prescribing in people with dementia. More data are needed on the benefits and harms of stopping medications in this population. Research should also test different approaches for supporting informed decision making about medications by people with dementia and caregivers.