Microscopic colitis syndrome consists of chronic watery diarrhea, a normal or near-normal gross appearance of the colonic mucosa, and a specific histologic picture described as either lymphocytic colitis or collagenous colitis. The cause of microscopic colitis is unknown, but recent work suggests some immunologic similarities to celiac disease, suggesting that luminal antigens may be important in its pathogenesis. Diarrhea in microscopic colitis seems to be directly related to the extent of inflammation, suggesting that inflammatory mediators are responsible for reduced water absorption by the colon. Microscopic colitis is a frequent diagnosis in patients with chronic diarrhea seen at referral centers. It is often associated with other immune-mediated conditions and frequently is complicated by fecal incontinence. The differential diagnosis is broad, comprising all causes of watery diarrhea. Evaluation is straightforward with the key aspect being review of colon biopsy specimens by an experienced pathologist. Treatment is still being defined: symptomatic management with antidiarrheal agents, 5-aminosalicylate drugs, corticosteroids, especially budesonide, bile acid-binding resins, and bismuth subsalicylate all can be effective. The prognosis is good with no evidence of conversion to classic inflammatory bowel disease or of development of neoplasia over time.