Although its definition has not been fully accepted, polypharmacy at advanced age appears as a significant worldwide problem in terms of both elderly health and general health systems and there are still many question marks / gaps with respect to this issue. We have insufficient data on its definition and thus its prevalence and complications. Non-prescription drugs are usually ignored in the studies. Health care professionals should be aware of the risks and interventions aiming to reduce exposure and minimizing the risk associated with potentially harmful drug combinations are needed. This article addresses these issues and proposes practical recommendations regarding the rational drug use for elderly age groups.