The clinical efficacy of probiotics and prebiotics has been proved in several clinical settings. The authors review their proved or potential side effects. Probiotics as living microorganisms may theoretically be responsible for 4 types of side effects in susceptible individuals: infections, deleterious metabolic activities, excessive immune stimulation, and gene transfer. Very few cases of infection have been observed. These occurred mainly in very sick patients who received probiotic drugs because of severe medical conditions. Prebiotics exert an osmotic effect in the intestinal lumen and are fermented in the colon. They may induce gaseousness and bloating. Abdominal pain and diarrhea only occur with large doses. An increase in gastroesophageal reflux has recently been associated with large daily doses. Tolerance depends on the dose and individual sensitivity factors (probably the presence of irritable bowel syndrome or gastroesophageal reflux), and may be an adaptation to chronic consumption.