Most of the antibiotic-associated diarrhea (AAD) cases result from a transient disturbance in the function of the normal intestinal flora and are spontaneously solved when discontinuing the antibacterial therapy. However, a mild diarrhea lasting several days may induce a dehydration or worsen a denutrition in frail elderly people.The incidence of AAD varies between 5 and 25% depending on the concerned antibiotic. Only 10-20% of all AAD cases are caused by infection, especially with Clostridium difficile, for which advanced age is a major risk factor. The first biological exam to perform when severe AAD or in frail people is the detection of C. difficile toxins, especially in elderly patient treated with beta-lactam antibiotics. Nevertheless, other infectious organisms causing AAD may be considered, as Staphylococcus aureus when predominant in stool cultures from patients treated with fluoroquinolones or as Klebsiella oxytoca when isolated in bloody diarrhea from patients treated with ampicillin. Elevated fecal counts of Candida spp. found in patients treated with antibiotics is rather the consequence of therapy than the cause of AAD. The prevention of AAD is based on a rational antibiotic use to avoid endogenous selection of C. difficile and on the improvement of the hygiene measures to limit the exogenous transmission of the bacteria or related spores by spoiled hands.Simultaneous prescription of non-pathogenic living organisms, capable of re-establishing the equilibrium of the intestinal flora, should be better described, especially in elderly people, because of its important economic impact.