Diarrhea is the leading cause of death in children younger than 5 years of age; persistent diarrhea accounts for 30 to 50 percent of those deaths in developing countries. Malnutrition, immunosuppression, young age, and an increase in the preceding diarrhea burdens are risk factors for the development of persistent diarrhea. Although many viruses, bacteria, and parasites can produce persistent diarrhea, enteropathogenic Escherichia coli, enteroaggregative E. coli, Giardia, Cryptosporidium, and Cyclospora are the most important of these agents. With currently available tests, identifying a specific cause usually is difficult. Newer sensitive molecular tests must be used for studying the epidemiology of persistent diarrhea in children. Management includes rehydration, adequate diet, micronutrient supplementation, and antimicrobials. Persistent diarrhea seriously affects nutritional status, growth, and intellectual function. Meeting these challenges is profoundly important, particularly in developing countries. © 2004 Elsevier Inc. All rights reserved.