Opinion statementWhen possible, patients taking nonsteroidal anti-inflammatory medications should discontinue them when the diagnosis of microscopic colitis is made. Although there is no direct evidence of its efficacy, a trial of elimination of caffeine or lactose or both should be undertaken.Nonspecific antidiarrheal agents (eg, loperamide, diphenoxylate) may be administered, but appear to be largely ineffective in this population.An aminosalicylate should be initiated at full therapeutic dose (2 to 4 g daily) as the first-line therapy. Because sulfasalazine appears to be associated with a high incidence of adverse effects in patients with microscopic colitis, other derivatives of 5-aminosalicylate (5-ASA) are preferred.Bile salt-binding agents such as cholestyramine or colestipol appear to be effective alternatives for patients who are either unresponsive to or intolerant of aminosalicylates.Systemic corticosteroids are an effective treatment for microscopic colitis, but may offer only transient improvement in symptoms. Given their potential adverse effects, corticosteroids should be reserved for patients with refractory disease in whom aminosalicylates and bile salt-binding agents have failed.Other agents that may be effective include antibiotics, bismuth subsalicylate, budesonide, pentoxifylline, octreotide, and methotrexate. Although these agents can be considered in unusual cases, the cumulative clinical experience with them in this setting is relatively limited.Surgical intervention, with either fecal stream diversion or subtotal colectomy, shows promise as an intervention of last resort.In refractory cases of microscopic colitis, strong consideration should be given to excluding a concomitant diagnosis of celiac disease, bacterial overgrowth, or chronic infection.