Older adults with dementia commonly have multiple chronic conditions that prompt clinicians to prescribe medications. While dementia is a life-limiting disease, progression from mild cognitive impairment to end stage dementia is a process that can occur over many years and may not take a predetermined course. Therefore aligning pharmacological treatment with changing goals of care can be challenging. The aim of this narrative review was to explore barriers to optimising prescribing and deprescribing (withdrawing) of medications as the goal of care shifts from prolonging life to optimising quality of life. Optimising pharmacological treatment to help people with dementia achieve their goals of care often requires deprescribing of medications that are inappropriate, as well as initiating appropriate medications. Medical practitioner, system, patient and carer related barriers to optimisation of medications in older adults with multiple morbidities have been identified including: inadequate guidelines, incomplete medical histories, lack of time, avoidance of negative consequences, established beliefs in the benefits and harms of medication use and others. Optimising prescribing for older people with dementia is further complicated by diminished decision making capacity, difficulties with comprehension and communication, increasing involvement of carers and difficulties establishing goals of care. Further research is required into the attitudes, beliefs and preferences of people with dementia and their carers regarding prescribing and deprescribing.