Ageing populations with multiple chronic conditions challenge low-, middle-, and high-income countries. Older adults frequently depend on complex medication regimens and polypharmacy, both of which can lead to potentially devastating and debilitating medication-related problems and to subsequent far-reaching public health, social, and economic effects. This perspectives article provides an overview of the current state of medication management, reflects on its relevance among polymedicated home-dwelling older adults living with multiple chronic conditions, and proposes patient-centered approaches for optimizing medication management and preventing medication-related problems.