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Diarrheal disease causes substantial morbidity and mortality worldwide; however, defining the microbiologic causes are challenging due to the large number of potential enteropathogens that require testing, insensitivity of existing conventional methods, the frequent occurrence of mixed infections, and high rates of background carriage in many communities.Here we review recent detection methods for enteropathogens with a particular focus on nucleic acid amplification assays.Nucleic acid amplification assays with high sensitivity and throughput now allow screening for multiple enteropathogens in stool samples. Interpretation will be complicated by high rates of mixed infections and background carriage in many communities. Therefore, new detection techniques, including quantitative methods, will need to be utilized in conjunction with the clinical context and careful study design. These methods should yield new insights into the causes and epidemiology of diarrhea.