The World Health Organization has highlighted that achieving medication without harm is their third global patient safety challenge. As more people are ageing worldwide, addressing this challenge is even more pertinent. When a person ages, age-related physiological changes impact their metabolism of medicines which may pose older people at a greater risk of experiencing medicine-related harm such as falls and hospitalisations. To understand how to reduce medicine-related risk and harm, it is vital to understand the underpinning concepts of ageing. This chapter provides an overview of the process of ageing and relatedly medicine-related harm in older people and specifically older people who identify as Australian First Nations people, Aboriginal and Torres Strait Islander people. Due to system-level barriers, Aboriginal and Torres Strait Islander people may experience health inequities. Therefore, we outline potential challenges pertaining to optimising medicine use in this group.