In the past 15 years, our knowledge of the pathogenesis and etiologic agents of diarrheal disease has expanded rapidly. No longer is it scientifically appropriate or cost effective for the laboratory simply to culture a stool for Salmonella and Shigella and to do a wet mount for amebae. Today we have a plethora of agents including, but not limited to, Campylobacter, Yersinia, Clostridium difficile, Escherichia coli, Aeromonas, Plesiomonas, vibrios, rotavirus, Norwalk agent, Giardia, and Cryptosporidium, which have all been suggested to be agents of diarrheal disease. Given such a wide range of possibilities, what approaches should be taken to determine the etiologic agent of diarrheal disease in the hospitalized patient in an era of cost containment?