World Health Organization (WHO) defines adverse drug reaction (ADR) as “a response to a drug which is noxious and unintended, and which occurs at doses normally used in man for the prophylaxis, diagnosis, or therapy of disease, or for the modifications of physiological function”. ADRs are a serious problem of contemporary pharmacotherapy. Expenditures for treatment of ADRs in the United States may cost up to 30.1 billion dollars annually. Factors affecting the development of ADRs are: age, gender, body weight, polypharmacy. About 10% of ADRs is associated with gastrointestinal tract (GIT). ADR can affect every part of GIT. Xerostomia is the most common ADR occurring in oral cavity. ADRs affecting esophagus include irritation and inflammation of the mucosa. Approximately one-third of all cases of esophageal inflammation results from administration of non-steroid anti-inflammatory drugs (NSAIDs). The main cause of ulcerations involving stomach and small intestine are NSAIDs. Drug-induced diarrheas are the most common adverse effect accounting for approximately 7% of all observed cases of ADRs. They may be triggered by antibiotics, magnesium salts, laxatives and others. On the other hand, some groups of medications may induce constipation. These drugs comprise opioids, diuretics, calcium channel blockers, cholinolytics and others. Proton pump inhibitors, metformin, orlistat and colesevelam may lead to restricted absorption of certain vitamins and minerals. Physicians’ knowledge about most popular and well documented ADRs can improve patients’ safety and make pharmacotherapy more comfortable for them.