Toxic megacolon (TM) is an infrequent but devastating complication of colitis. Numerous forms of colonic inflammation can give rise to TM but the majority occur in individuals with inflammatory bowel disease (IBD). Recently there has been a marked increase in the number of reports of TM associated with pseudomembranous colitis. Because of the associated high morbidity and mortality, early recognition and management of TM is of paramount importance. The mechanisms involved in development of TM are not clearly delineated, but chemical mediators such as nitric oxide and interleukins may play a pivotal role in the pathogenesis. New evidence suggests that TM and its associated morbidity may be predicted by the extent of small bowel and gastric distension in patients with colitis. CT scanning may also play an important role the management of TM, in that it may be the only noninvasive mode to detect subclinical perforations and abscesses. Management involves close medical attention, supportive care, and treatment of the underlying colitis. Possible exacerbating factors such as narcotic and anticholinergic medications must be withdrawn, and colonic decompression via tube drainage or positional techniques must be considered. Signs of progression or complications of the disease must be treated aggressively with surgical intervention, as delay is associated with even greater risk of mortality.