Antidepressants are increasingly used in Poland and around The World. Over recent years, new antidepressants have appeared that are safer and better tolerated, but side effects remain a significant clinical problem that complicates achieving full remission. During pharmacotherapy with antidepressants, we should pay attention to the appropriate selection of the drug (from the medical point of view), but also to the patient’s beliefs regarding the treatment (from the psychological point of view). It is also important to remember to take into account patient’s psychiatric and somatic co-morbidities and to collect all informations about current medication taken by patient in order to avoid unfavorable pharmacological interactions. If complaints about side effects occur, it is necessary to differentiate whether they effects result from biological or psychological factor. This allows you to make more conscious and effective decisions in everyday medical practice. The article discusses biological factors such as cytochrome P450 polymorphism, coexistence of ADHD, drug interactions and psychological factors influencing more frequent and unusual side effects of antidepressants.