Microscopic colitis (MC) is diagnosed in up to 13% of patients investigated for chronic diarrhea, particularly in middle-aged and elderly patients. Recent studies have suggested an etiological role for various drugs, including nonsteroidal anti-inflammatory drugs and proton pump inhibitors. To ascertain the potential role for drug exposure in the development of MC, we performed a systematic review based on a MEDLINE search and conducted a meta-analyses on the available data. We also give an overview of the case reports and studies illustrating the role of drugs in inducing MC. A number of hypotheses are formulated with regard to the potential pathophysiological mechanisms in drug-induced MC. However, confirmative evidence is still largely lacking. Considering the high number of drug users and the relatively low incidence of MC, it is more likely that drug-induced cases of MC are the result of an idiosyncratic reaction.