At present, pharmacotherapy leading to a reduction in hydrochloric acid production in the stomach constitutes the core treatment strategy for the majority of the upper intestinal tract diseases. Proton pump inhibitors (PPIs) are the predominant therapeutic group. Gastroesophageal reflux disease is the main indication for the long-term PPI use. Chronic use might be associated with adverse reactions. Potential risks take a form of malabsorption of certain food nutrients with their consequent deficiency, bacterial overgrowth and increased incidence of infections as well as altered regulation of proliferation of gastric as well as other mucosas. Individual risks are low; their assessment is mostly based on the results of population studies. Even though the treatment benefits outweigh any potential theoretical risks, it is wise to decide well on the correct indication and to prescribe the lowest effective dose.