It is postulated that minimizing anticholinergic burden in older people may result in improved short-term memory and behavior, reduced confusion and delirium, and enhanced quality of life and daily functioning. The purpose of this opinion article was to investigate the current trends and future implications relating to the examination and estimation of anticholinergic burden in older people. Current evidence linking medicines with anticholinergic activity and cognitive impairment is derived mostly from observational data. Further research with larger trials or cohort studies with adequate power and appropriate follow-up periods is required to confirm associations between anticholinergic burden and adverse outcomes. This article provides insights into different approaches for the estimation of anticholinergic burden. Network-based systems pharmacology models could be an effective way of understanding anticholinergic drug-induced adverse effects. The emphasis on mechanistic models may open new opportunities for researchers to understand adverse drug effects in clinical practice. In the interim, medicines with high anticholinergic activity should be avoided in older people, unless considered clinically essential. In this instance, they should be used at a low/titrated dose and for the shortest duration possible. It is therefore important to reinforce the clinical significance of reviewing anticholinergic medicines in older people.