Older adults face unique medication therapy challenges due to interactions between physiological effects of aging, multimorbidity, and polypharmacy, termed multicomplexity. These result in high rates of medication adverse effects and treatment failures as a result of pharmacokinetic changes, pharmacodynamic changes, and geriatric syndromes. Interprofessional care and multimodal strategies are necessary, and despite clinical decision support tools available, optimal outcomes remain difficult to achieve.