Pharmacovigilance is defined as "the detection, evaluation, understanding and prevention of adverse drug reactions (ADRs)". The ultimate aim of pharmacovigilance is the optimization of the risk-benefit ratio of marketed drugs at the individual level (i.e. the choice of the most suitable treatment for a given patient) and at the population level (i.e. maintenance or removal of a drug from the market, informing prescribers of its potential risks, etc.). Prevalence of drug-related morbidity and mortality increase in correlation with the increase in drug use. Both physicians and patients prefer polypharmacy because of different reasons such as insufficient knowledge, lack of enough time for the patients, being misled by non-scientific newspaper/TV news, etc. Polypharmacy is among the major causes of drug-related morbidity and requires additional medication as treatment. On the other hand, adverse reactions might be minimized by adequate knowledge and rational prescribing, simply by reducing inappropriate polypharmacy. Therefore, physicians' prescribing habits based on rational pharmacotherapy processes which include choosing suitable drug(s), at an optimum dose and duration of use, among the effective and safe treatment alternatives, and informing patients about the diagnosis and treatment, can be a major contribution to optimize the risk-benefit ratio of drugs. As an essential step in the rational pharmacotherapy process, giving adequate information to the patients about their treatment (i.e. dosage, use instructions, warnings, effects, side effects, etc.) may prevent some of the drug-related problems. In addition, informed patients are more likely to seek advice from their physicians to seek advice for ADRs. In this review article, therefore, the influence of rational pharmacotherapy training on the pharmacovigilance of drugs will be discussed.