Diverticular disease of the colon is a common health problem in western societies. Most patients with colonic diverticula are asymptomatic; it has been estimated that only 20% of individuals harboring diverticula will develop symptoms and signs of illness and a minority will develop major complications. Although the efficacy of a high fiber diet in the management of symptomatic uncomplicated diverticular disease is still controversial, bran and bulking agents are commonly used. Antibiotics are used to treat major inflammatory complications of diverticular disease but apparently there is no rationale for the use of antibiotics in uncomplicated disease where an inflammatory component is by definition excluded. In a multicenter open trial, 217 patients with symptomatic uncomplicated diverticular disease were treated with glucomannan (110 pts) or with glucomannan plus a poorly absorbable antibiotic (rifaximin 400 mg bid for 7 days each month) (107 pts). Clinical evaluation was performed bimonthly for 12 months using a global score system for 8 clinical variables. After 12 months, patients treated with glucomannan plus rifaximin showed a 63.9% reduction of the score as compared to 47.6% in patients treated with glucomannan only (p < 0.001). Cyclic administration of rifaximin appears to be of some advantage in obtaining symptomatic relief in uncomplicated diverticular disease.