The growth of the aging population leads to the increase of chronic diseases, of the burden of multimorbility, and of the complexity polypharmacy. The prevalence of medication errors rises in patients with polypharmacy in primary care, and this is a major concern to healthcare systems. This study reviews the published literature on the inappropriate use of medicines in order to articulate recommendations on how to reduce it in chronic patients, particularly in those who are elderly, polymedicated, or multipathological. A systematic review of articles published from January 2000 to October 2015 was performed using MEDLINE, EMBASE, PsychInfo, Scopus, The Cochrane Library, and Index Medicus databases. We selected 80 studies in order to analyse the content that addressed the question under consideration. Our literature review found that half of patients know what their prescribed treatment is; that most of elderly people take five or more medications a day; that in elderly, polymedicated people, the probability of a medication error occurring is higher; that new tools have been recently developed to reduce errors; that elderly patients can understand written information but the presentation and format is an important factor; and that a high percentage of patients have remaining doubts after their visit. Thus, strategies based on the evidence should be applied in order to reduce medication errors.