Polypharmacy characterizes ongoing prescription of multiple medications in a patient. Following the demographic change and growing number of elderly patients, polypharmacy is of major concern due to the associated risks and even mortality. Many causes made this geriatric syndrome more common in the past decade. First, the management of comorbidities is often lacking in disease-specific guidelines. Second, multimorbidity is rising due to the ageing population. Third, deprescribing methods are sparse, and results are conflicting. This mini review integrates the effects of polypharmacy on mortality and morbidity, the causes and confounders of polypharmacy, and presents a practical stepwise manual of deprescribing. The work is based on a literature search for randomized control trials and reviews in English and German from 2015 onwards in the PubMed database, with integration of relevant citations as a result of this search.