Summary: Prokinetics are widely used in the treatment of the upper digestive tract functional diseases, but they may also have beneficial effect on motility disorders of the distal part of the digestive tract. Normal physiological peristalsis is one of the factors playing important role in prevention of colonization of the small intestine by colonic microbiota and development of small intestinal bacterial overgrowth (SIBO). A wide range of predisposing factors include surgical procedures and diseases affecting intestinal motility, such as hypothyroidism, Parkinson’s disease or diabetes mellitus. Most studies have suggested an association between protonpump inhibitors (PPIs) use and increased risk of SIBO, although some have not confirm this relationship. Latest studies indicate potential benefits from prokinetics use not only in reducing the risk of developing SIBO, but also in its treatment. The benefits of adding prokinetics to PPIs have been described in patients treated mainly for gastroesophageal reflux disease in whom significantly lower occurrence of SIBO has been observed after addition of the prokinetic drug. Promising results have been also obtained in the study analyzing the efficacy of prokinetics in the treatment of patients with SIBO and IBS, as well as in the therapy of cirrhotic patients with ascites, accompanied by SIBO development. Beneficial effects of prokinetics have been also observed in patients with acute colonic pseudo obstruction and in pharmacological therapy of feed intolerance in the critically ills. Despite of promising preliminary results of recently published studies, further multicenter, randomized trials are needed to assess efficacy and safety of such treatment.