The UK population is ageing rapidly, a trend that is likely to continue due to improvements in chronic disease management and increased life expectancy. Comorbidities, including frailty, become increasingly common with age and as a result it is likely that multiple medicines will be prescribed for older people, leading to polypharmacy. This is a concern because polypharmacy is associated with various adverse effects and an increased medicine burden in this population, as well as a financial burden for the healthcare system. This article, the first of two parts, explains the physiology of ageing and frailty, and considers the adverse effects of polypharmacy on older people with frailty, using a fictional case study to illustrate this. Part two will use the case study to explore the use of medication reviews and deprescribing benefits as part of medicines optimisation.